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BS in Pharmacy and Biochemistry from the University of São Paulo (USP), Brazil. M.Sc. in Technology of Fermentation and Ph.D. in Life Sciences (Biochemistry) both from the USP. Associate professor in the Institute of Marine Sciences at the Federal University of Ceará. He teaches environmental chemistry, pollution science, molecular biology, and pharmaceutical biotechnology. His main scientific interests are polypeptides from terrestrial and marine organisms, cell receptors, molecular interaction, and recombinant DNA technology.
The occurrence of pharmaceuticals in the environment is an everyday recognized concern worldwide, and drugs as environmental contaminants have been detected in water and soil systems, posing risks to humans and wildlife. The presence of drugs in wastewater, groundwater, and even drinking water occurs in several countries, including Brazil, where the pharmaceutical market is expanding over the years. The adverse, harmful effects of pharmaceuticals in the environment range from the spreading of antimicrobial resistance and species survival to the interference with reproduction and increased cancer incidence in humans. Therefore, it is demanding to count on proper legislation to prevent these pollutants from entering the distinct environment compartments. In some developed countries, laws, directives, programs, and initiatives regarding drug disposal reach a mature status. In Brazil, federal laws dealing with drug residues’ management are recent, with flaws that might facilitate non-compliance with drug pollution issues. Besides, pharmacies and drugstores are not obligated to collect unneeded household medicines, while particular State laws aim to ordinate the disposal of drug residues regionally. In this review, we consider the current knowledge about pharmaceutical (drug) pollution, the recommendation and regulations on the disposal of useless medicines in some countries, and in the context of the expanding pharmaceutical market in Brazil. The awareness of emerging contaminants in the environment, besides the joint effort of authorities, consumers, and the general public nationwide, will be required to avoid pharmaceutical/drug pollution and achieve an eco-friendly environment and a sustainable society.
Letícia Freitas; Gandhi Radis-Baptista. Pharmaceutical Pollution and Disposal of Expired, Unused, and Unwanted Medicines in the Brazilian Context. Journal of Xenobiotics 2021, 11, 61 -76.
AMA StyleLetícia Freitas, Gandhi Radis-Baptista. Pharmaceutical Pollution and Disposal of Expired, Unused, and Unwanted Medicines in the Brazilian Context. Journal of Xenobiotics. 2021; 11 (2):61-76.
Chicago/Turabian StyleLetícia Freitas; Gandhi Radis-Baptista. 2021. "Pharmaceutical Pollution and Disposal of Expired, Unused, and Unwanted Medicines in the Brazilian Context." Journal of Xenobiotics 11, no. 2: 61-76.
Background: Crotalicidin (Ctn), a snake venom cathelicidin-related antimicrobial peptide, is a 34-residue-long linear lysine-rich vipericidin obtained from the South American rattlesnake, Crotalus durissus terrificus. Ctn contains tandem repeats of nine amino acid residues (1KRFKKFFKK9 and 16KRLKKIFKK24; consensus: 1KRhKKhFKK9, h = hydrophobic amino acid) as an integral part of its structure. Objective: The aim of this study was to evaluate the antimicrobial activity of the encrypted vipericidin nonapeptide KRFKKFFKK, designated as Ctn[1-9], and its structural analogue, rhodamine-B‒conjugated Ctn[1-9], designated as RhoB-Ctn[1-9]. Method: The susceptibility of representative pathogenic bacteria and yeasts to antimicrobial agents was determined using the broth microdilution minimum inhibitory concentration (MIC) method. Cytotoxicity was estimated using a hemolytic assay. The accumulation of RhoB-Ctn[1-9] in microbial cells was observed by fluorescence microscopy. The antimicrobial synergism of RhoB-Ctn[1-9] with antimicrobials was evaluated using a checkerboard analysis. Results: RhoB-conjugated Ctn[1-9] displayed selective antimicrobial activity against infectious gram-negative bacteria such as Escherichia coli, Pseudomonas aeruginosa, and pathogenic species of Candida with low hemolytic effects on human erythrocytes which was not observed with unconjugated Ctn[1-9]. RhoB-Ctn[1-9] could permeate cell membranes and accumulate intracellularly in microbial cells. RhoB-Ctn[1-9] exhibits synergistic effects when used with antibiotics or antifungal agents and reduced the MICs of the peptide and antimicrobials. Conclusion: These findings indicate the potential of crotalicidin-related short peptides as structural motifs for the diversification of biological functionalities. Further, they set the stage to investigate the molecular mechanisms by which chemically modified vipericidin repeats modulate cell fate.
Hilania Valeria Doudou Lima; Thales Márcio Cabral dos Santos; Mirelly Mirna Alves de Sousa Silva; João Victor Da Silva Albuquerque; Luciana Magalhães Melo; Vicente José De Figueirêdo Freitas; Gandhi Rádis-Baptista. The Rhodamine B-encrypted vipericidin peptide, RhoB-Ctn[1-9], displays in vitro antimicrobial activity against opportunistic bacteria and yeasts. Current Pharmaceutical Biotechnology 2021, 22, 1 -1.
AMA StyleHilania Valeria Doudou Lima, Thales Márcio Cabral dos Santos, Mirelly Mirna Alves de Sousa Silva, João Victor Da Silva Albuquerque, Luciana Magalhães Melo, Vicente José De Figueirêdo Freitas, Gandhi Rádis-Baptista. The Rhodamine B-encrypted vipericidin peptide, RhoB-Ctn[1-9], displays in vitro antimicrobial activity against opportunistic bacteria and yeasts. Current Pharmaceutical Biotechnology. 2021; 22 ():1-1.
Chicago/Turabian StyleHilania Valeria Doudou Lima; Thales Márcio Cabral dos Santos; Mirelly Mirna Alves de Sousa Silva; João Victor Da Silva Albuquerque; Luciana Magalhães Melo; Vicente José De Figueirêdo Freitas; Gandhi Rádis-Baptista. 2021. "The Rhodamine B-encrypted vipericidin peptide, RhoB-Ctn[1-9], displays in vitro antimicrobial activity against opportunistic bacteria and yeasts." Current Pharmaceutical Biotechnology 22, no. : 1-1.
Cell-penetrating peptides (CPPs) comprise a class of short polypeptides that possess the ability to selectively interact with the cytoplasmic membrane of certain cell types, translocate across plasma membranes and accumulate in the cell cytoplasm, organelles (e.g., the nucleus and mitochondria) and other subcellular compartments. CPPs are either of natural origin or de novo designed and synthesized from segments and patches of larger proteins or designed by algorithms. With such intrinsic properties, along with membrane permeation, translocation and cellular uptake properties, CPPs can intracellularly convey diverse substances and nanomaterials, such as hydrophilic organic compounds and drugs, macromolecules (nucleic acids and proteins), nanoparticles (nanocrystals and polyplexes), metals and radionuclides, which can be covalently attached via CPP N- and C-terminals or through preparation of CPP complexes. A cumulative number of studies on animal toxins, primarily isolated from the venom of arthropods and snakes, have revealed the cell-penetrating activities of venom peptides and toxins, which can be harnessed for application in biomedicine and pharmaceutical biotechnology. In this review, I aimed to collate examples of peptides from animal venoms and toxic secretions that possess the ability to penetrate diverse types of cells. These venom CPPs have been chemically or structurally modified to enhance cell selectivity, bioavailability and a range of target applications. Herein, examples are listed and discussed, including cysteine-stabilized and linear, α-helical peptides, with cationic and amphipathic character, from the venom of insects (e.g., melittin, anoplin, mastoparans), arachnids (latarcin, lycosin, chlorotoxin, maurocalcine/imperatoxin homologs and wasabi receptor toxin), fish (pardaxins), amphibian (bombesin) and snakes (crotamine and cathelicidins).
Gandhi Rádis-Baptista. Cell-Penetrating Peptides Derived from Animal Venoms and Toxins. Toxins 2021, 13, 147 .
AMA StyleGandhi Rádis-Baptista. Cell-Penetrating Peptides Derived from Animal Venoms and Toxins. Toxins. 2021; 13 (2):147.
Chicago/Turabian StyleGandhi Rádis-Baptista. 2021. "Cell-Penetrating Peptides Derived from Animal Venoms and Toxins." Toxins 13, no. 2: 147.
Hilania V. Dodou Lima; Carolina Sidrim De Paula Cavalcante; Gandhi Rádis-Baptista. Corrigendum to “Antimicrobial activity of synthetic Dq-3162, a 28-residue ponericin G-like dinoponeratoxin from the giant ant Dinoponera quadriceps venom, against carbapenem-resistant bacteria” [Toxicon 187 November 2020 19–28]. Toxicon 2020, 189, 105 -106.
AMA StyleHilania V. Dodou Lima, Carolina Sidrim De Paula Cavalcante, Gandhi Rádis-Baptista. Corrigendum to “Antimicrobial activity of synthetic Dq-3162, a 28-residue ponericin G-like dinoponeratoxin from the giant ant Dinoponera quadriceps venom, against carbapenem-resistant bacteria” [Toxicon 187 November 2020 19–28]. Toxicon. 2020; 189 ():105-106.
Chicago/Turabian StyleHilania V. Dodou Lima; Carolina Sidrim De Paula Cavalcante; Gandhi Rádis-Baptista. 2020. "Corrigendum to “Antimicrobial activity of synthetic Dq-3162, a 28-residue ponericin G-like dinoponeratoxin from the giant ant Dinoponera quadriceps venom, against carbapenem-resistant bacteria” [Toxicon 187 November 2020 19–28]." Toxicon 189, no. : 105-106.
Ctn[15–34], the C-terminal fragment of crotalicidin, an antimicrobial peptide from the South American rattlesnake Crotalus durissus terrificus venom, displays remarkable anti-infective and anti-proliferative activities. Herein, its activity on Candida albicans biofilms and its interaction with the cytoplasmic membrane of the fungal cell and with a biomembrane model in vitro was investigated. A standard C. albicans strain and a fluconazole-resistant clinical isolate were exposed to the peptide at its minimum inhibitory concentration (MIC) (10 µM) and up to 100 × MIC to inhibit biofilm formation and its eradication. A viability test using XTT and fluorescent dyes, confocal laser scanning microscopy, and atomic force microscopy (AFM) were used to observe the antibiofilm effect. To evaluate the importance of membrane composition on Ctn[15–34] activity, C. albicans protoplasts were also tested. Fluorescence assays using di-8-ANEPPS, dynamic light scattering, and zeta potential measurements using liposomes, protoplasts, and C. albicans cells indicated a direct mechanism of action that was dependent on membrane interaction and disruption. Overall, Ctn[15–34] showed to be an effective antifungal peptide, displaying antibiofilm activity and, importantly, interacting with and disrupting fungal plasma membrane.
Francisca Aguiar; Nuno Santos; Carolina De Paula Cavalcante; David Andreu; Gandhi Baptista; Sónia Gonçalves. Antibiofilm Activity on Candida albicans and Mechanism of Action on Biomembrane Models of the Antimicrobial Peptide Ctn[15–34]. International Journal of Molecular Sciences 2020, 21, 8339 .
AMA StyleFrancisca Aguiar, Nuno Santos, Carolina De Paula Cavalcante, David Andreu, Gandhi Baptista, Sónia Gonçalves. Antibiofilm Activity on Candida albicans and Mechanism of Action on Biomembrane Models of the Antimicrobial Peptide Ctn[15–34]. International Journal of Molecular Sciences. 2020; 21 (21):8339.
Chicago/Turabian StyleFrancisca Aguiar; Nuno Santos; Carolina De Paula Cavalcante; David Andreu; Gandhi Baptista; Sónia Gonçalves. 2020. "Antibiofilm Activity on Candida albicans and Mechanism of Action on Biomembrane Models of the Antimicrobial Peptide Ctn[15–34]." International Journal of Molecular Sciences 21, no. 21: 8339.
The predatory giant ant Dinoponera quadriceps is one of the largest venomous ants on Earth. The venom of D. quadriceps comprises a rich blend of bioactive peptides that includes structures related to at least five classes of antimicrobial peptides. In the present study, two representative synthetic peptides, sDq-2562 and sDq-3162, belonging to the ponericin-like dinoponeratoxin family, were evaluated for their microbicide activity against antibiotic-resistant bacteria. The most effective peptide, the 28-residue sDq-3162 displayed a significant bacteriostatic and bactericidal effect with minimal inhibitory concentrations (MICs) between 5 μM and 10 μM (15.6 μg mL−1 and 31.2 μg mL−1), according to the strain of drug-resistant bacteria tested. In combination with conventional antibiotics, sDq-3162 displayed in vitro synergistic effects, reducing the MICs of antibiotics for more than 2-log against clinical isolates of carbapenem-resistant Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa, with low cytotoxicity to human erythrocytes, in vitro. Since the development of molecules to circumvent the spread of antibiotic-resistant bacteria is demanding, ant venom peptides arise as useful molecular resources to contribute with the antimicrobial arsenal and therapeutic strategies to fight clinically relevant microbial infections.
Hilania V. Dodou Lima; Carolina Sidrim De Paula Cavalcante; Gandhi Rádis-Baptista. Antimicrobial activity of synthetic Dq-3162, a 28-residue ponericin G-like dinoponeratoxin from the giant ant Dinoponera quadriceps venom, against carbapenem-resistant bacteria. Toxicon 2020, 187, 19 -28.
AMA StyleHilania V. Dodou Lima, Carolina Sidrim De Paula Cavalcante, Gandhi Rádis-Baptista. Antimicrobial activity of synthetic Dq-3162, a 28-residue ponericin G-like dinoponeratoxin from the giant ant Dinoponera quadriceps venom, against carbapenem-resistant bacteria. Toxicon. 2020; 187 ():19-28.
Chicago/Turabian StyleHilania V. Dodou Lima; Carolina Sidrim De Paula Cavalcante; Gandhi Rádis-Baptista. 2020. "Antimicrobial activity of synthetic Dq-3162, a 28-residue ponericin G-like dinoponeratoxin from the giant ant Dinoponera quadriceps venom, against carbapenem-resistant bacteria." Toxicon 187, no. : 19-28.
Venoms from ants comprise a rich source of bioactive peptides, including antimicrobial peptides. From the proteome and peptidome of the giant ant Dinoponera quadriceps venom, members of five known classes of antimicrobial peptides were disclosed (e.g., dermaseptin-, defensin-, ICK-, pilosulin- and ponericin-like types). Based on comparative analysis, these family members have structural determinants that indicate they could display antimicrobial activities. In previous works, pilosulin- and ponericin-like peptides were demonstrated to be active against bacteria, fungi, and parasites. Herein, the antifungal activity of ponericin- and pilosulin-like peptides were assessed, aiming at the expansion of the knowledge about AMPs in predatory ants and the development of new microbicide strategies to deal with difficult-to-treat fungal infections. Synthetic pilosulin- (Dq-2562, Dq-1503, and Dq-1319) and ponericin-like (Dq-3162) peptides were evaluated for their fungicide and fungistatic activities against different species of Candida, including a drug-resistant clinical strain. The MICs and MLCs were determined for all peptides individually and in combination with general antifungal drugs by the microdilution method. The time-kill kinetic curves were set up by means of a luminescent reagent, of which the light signal is proportional to the number of viable cells. The candicidal synergism observed by the combination of subinhibitory concentrations of peptides and general antimycotic drugs were quantified by the checkerboard test and fluorescent dye permeation assay. The influence of ergosterol on the antifungal activity was verified by supplementation of culture medium. The pilosulin- (Dq-2562 and Dq-1503) and ponericin-like (Dq-3162) were the most active peptides, displaying a broad spectrum of antifungal activity in vitro, with MICs in the range of 0.625 to 10 µM. The combination of peptides and conventional antimycotic drugs displayed a synergistic reduction in the MIC values of individual peptides and drugs, while soluble ergosterol in the culture medium increased the MICs. The fungicide and fungistatic activity of the individual peptides and peptides in combination with antimycotics were time-dependent with a rapid onset of action and long-lasting effect, which involved membrane disruption as an underlying mechanism of their action. Altogether, pilosulin- and ponericin-like peptides from the giant ant D. quadriceps venom display a broad-spectrum of candicidal activity, what allows their inclusion in the row of the antifungal peptides and gives support for further studies on the development of strategies to fight candidiasis.
Hilania Valéria Dodou Lima; Carolina Sidrim De Paula Cavalcante; Gandhi Rádis-Baptista. Antifungal In Vitro Activity of Pilosulin- and Ponericin-Like Peptides from the Giant Ant Dinoponera quadriceps and Synergistic Effects with Antimycotic Drugs. Antibiotics 2020, 9, 354 .
AMA StyleHilania Valéria Dodou Lima, Carolina Sidrim De Paula Cavalcante, Gandhi Rádis-Baptista. Antifungal In Vitro Activity of Pilosulin- and Ponericin-Like Peptides from the Giant Ant Dinoponera quadriceps and Synergistic Effects with Antimycotic Drugs. Antibiotics. 2020; 9 (6):354.
Chicago/Turabian StyleHilania Valéria Dodou Lima; Carolina Sidrim De Paula Cavalcante; Gandhi Rádis-Baptista. 2020. "Antifungal In Vitro Activity of Pilosulin- and Ponericin-Like Peptides from the Giant Ant Dinoponera quadriceps and Synergistic Effects with Antimycotic Drugs." Antibiotics 9, no. 6: 354.
Ants (Hymenoptera, Apocrita, Aculeata, Formicoidea) comprise a well-succeeded group of animals. Like bees and wasps, ants are mostly venomous, having a sting system to deliver a mixture of bioactive organic compounds and peptides. The predatory giant ant Dinoponera quadriceps belongs to the subfamily Ponerinae that includes one of the largest known ant species in the world. In the present study, low molecular weight compounds and peptides were identified by online peptide mass fingerprint. These include neuroactive biogenic amines (histamine, tyramine, and dopamine), monoamine alkaloid (phenethylamine), free amino acids (e.g. glutamic acid and proline), free thymidine, and cytosine. To the best of our knowledge, most of these components are described for the first time in an ant venom. Multifunctional dinoponeratoxin peptide variants (pilosulin- and ponericin-like peptides) were characterized that possess antimicrobial, hemolytic, and histamine-releasing properties. These venom components, particularly peptides, might synergistically contribute to the overall venom activity and toxicity, for immobilizing live prey, and for defending D. quadriceps against aggressors, predators, and potential microbial infection.
Gandhi Rádis-Baptista; Hilania V. Dodou; Álvaro R.B. Prieto-Da-Silva; André J. Zaharenko; Kohei Kazuma; Ken-Ichi Nihei; Hidetoshi Inagaki; Kanami Mori-Yasumoto; Katsuhiro Konno. Comprehensive analysis of peptides and low molecular weight components of the giant ant Dinoponera quadriceps venom. Biological Chemistry 2020, 401, 945 -954.
AMA StyleGandhi Rádis-Baptista, Hilania V. Dodou, Álvaro R.B. Prieto-Da-Silva, André J. Zaharenko, Kohei Kazuma, Ken-Ichi Nihei, Hidetoshi Inagaki, Kanami Mori-Yasumoto, Katsuhiro Konno. Comprehensive analysis of peptides and low molecular weight components of the giant ant Dinoponera quadriceps venom. Biological Chemistry. 2020; 401 (8):945-954.
Chicago/Turabian StyleGandhi Rádis-Baptista; Hilania V. Dodou; Álvaro R.B. Prieto-Da-Silva; André J. Zaharenko; Kohei Kazuma; Ken-Ichi Nihei; Hidetoshi Inagaki; Kanami Mori-Yasumoto; Katsuhiro Konno. 2020. "Comprehensive analysis of peptides and low molecular weight components of the giant ant Dinoponera quadriceps venom." Biological Chemistry 401, no. 8: 945-954.
Venom-derived peptides display diverse biological and pharmacological activities, making them useful in drug discovery platforms and for a wide range of applications in medicine and pharmaceutical biotechnology. Due to their target specificities, venom peptides have the potential to be developed into biopharmaceuticals to treat various health conditions such as diabetes mellitus, hypertension, and chronic pain. Despite the high potential for drug development, several limitations preclude the direct use of peptides as therapeutics and hamper the process of converting venom peptides into pharmaceuticals. These limitations include, for instance, chemical instability, poor oral absorption, short halflife, and off-target cytotoxicity. One strategy to overcome these disadvantages relies on the formulation of bioactive peptides with nanocarriers. A range of biocompatible materials are now available that can serve as nanocarriers and can improve the bioavailability of therapeutic and venom-derived peptides for clinical and diagnostic application. Examples of isolated venom peptides and crude animal venoms that have been encapsulated and formulated with different types of nanomaterials with promising results are increasingly reported. Based on the current data, a wealth of information can be collected regarding the utilization of nanocarriers to encapsulate venom peptides and render them bioavailable for pharmaceutical use. Overall, nanomaterials arise as essential components in the preparation of biopharmaceuticals that are based on biological and pharmacological active venom-derived peptides.
Ana Paula Dos Santos; Tamara Goncalves De Araujo; Gandhi Radis Baptista. Nanoparticles Functionalized with Venom-Derived Peptides and Toxins for Pharmaceutical Applications. Current Pharmaceutical Biotechnology 2020, 21, 97 -109.
AMA StyleAna Paula Dos Santos, Tamara Goncalves De Araujo, Gandhi Radis Baptista. Nanoparticles Functionalized with Venom-Derived Peptides and Toxins for Pharmaceutical Applications. Current Pharmaceutical Biotechnology. 2020; 21 (2):97-109.
Chicago/Turabian StyleAna Paula Dos Santos; Tamara Goncalves De Araujo; Gandhi Radis Baptista. 2020. "Nanoparticles Functionalized with Venom-Derived Peptides and Toxins for Pharmaceutical Applications." Current Pharmaceutical Biotechnology 21, no. 2: 97-109.
Arthropods comprise a predominant and well-succeeded phylum of the animal kingdom that evolved and diversified in millions of species grouped in four subphyla, namely, Chelicerata (arachnids), Crustacea, Myriapoda (centipedes), and Hexapoda (insects)
Gandhi Rádis-Baptista; Katsuhiro Konno. Arthropod Venom Components and Their Potential Usage. Toxins 2020, 12, 82 .
AMA StyleGandhi Rádis-Baptista, Katsuhiro Konno. Arthropod Venom Components and Their Potential Usage. Toxins. 2020; 12 (2):82.
Chicago/Turabian StyleGandhi Rádis-Baptista; Katsuhiro Konno. 2020. "Arthropod Venom Components and Their Potential Usage." Toxins 12, no. 2: 82.
A global public health crisis has emerged with the extensive dissemination of multidrug-resistant microorganisms. Antimicrobial peptides (AMPs) from plants and animals have represented promising tools to counteract those resistant pathogens due to their multiple pharmacological properties such as antimicrobial, anticancer, immunomodulatory and cell-penetrating activities. In this review, we will focus on crotamine and crotalicidin, which are two interesting examples of membrane active peptides derived from the South America rattlesnake Crotalus durrisus terrificus venom. Their full-sequences and structurally-minimized fragments have potential applications, as anti-infective and anti-proliferative agents and diagnostics in medicine and in pharmaceutical biotechnology.
Claudio Borges Falcao; Gandhi Radis-Baptista. Crotamine and crotalicidin, membrane active peptides from Crotalus durissus terrificus rattlesnake venom, and their structurally-minimized fragments for applications in medicine and biotechnology. Peptides 2019, 126, 170234 .
AMA StyleClaudio Borges Falcao, Gandhi Radis-Baptista. Crotamine and crotalicidin, membrane active peptides from Crotalus durissus terrificus rattlesnake venom, and their structurally-minimized fragments for applications in medicine and biotechnology. Peptides. 2019; 126 ():170234.
Chicago/Turabian StyleClaudio Borges Falcao; Gandhi Radis-Baptista. 2019. "Crotamine and crotalicidin, membrane active peptides from Crotalus durissus terrificus rattlesnake venom, and their structurally-minimized fragments for applications in medicine and biotechnology." Peptides 126, no. : 170234.
Ants (Hymenoptera, Apocrita, Aculeata, Formicoidea) comprise a well-succeeded group of animals. Like bees and wasps, ants are mostly venomous, having a sting system to deliver a mixture of bioactive organic compounds and peptides. The predatory giant ant Dinoponera quadriceps belongs to the subfamily Ponerinae that include one of the largest known ant species in the world. In the present study, low molecular weight compounds and peptides were identified by on-line peptide mass fingerprint. These include neuroactive biogenic amines (histamine, tyramine, and dopamine), monoamine alkaloid (phenethylamine), free amino acids (e.g., glutamic acid and proline), free thymidine and cytosine. To the best of our knowledge most of these components are described for the first time in an ant venom. Multifunctional dinoponeratoxin peptides variants (pilosulin- and ponericin-like peptides) were characterized that possess antimicrobial, hemolytic, and histamine-releasing properties. These venom components, particularly peptides, might synergistically contribute to the overall venom activity and toxicity, for immobilizing live prey, and defending D. quadriceps against aggressors, predators and potential microbial infection.
Gandhi Rádis-Baptista; Hilania V. Dodou; Álvaro R. B. Prieto-Da-Silva; André J. Zaharenko; Kohei Kazuma; Ken-Ichi Nihei; Hidetoshi Inagaki; Kanami Mori-Yasumoto; Katsuhiro Konno. Comprehensive analysis of peptides and low molecular weight components of the giant ant Dinoponera quadriceps venom. Biological Chemistry 2019, 1 .
AMA StyleGandhi Rádis-Baptista, Hilania V. Dodou, Álvaro R. B. Prieto-Da-Silva, André J. Zaharenko, Kohei Kazuma, Ken-Ichi Nihei, Hidetoshi Inagaki, Kanami Mori-Yasumoto, Katsuhiro Konno. Comprehensive analysis of peptides and low molecular weight components of the giant ant Dinoponera quadriceps venom. Biological Chemistry. 2019; ():1.
Chicago/Turabian StyleGandhi Rádis-Baptista; Hilania V. Dodou; Álvaro R. B. Prieto-Da-Silva; André J. Zaharenko; Kohei Kazuma; Ken-Ichi Nihei; Hidetoshi Inagaki; Kanami Mori-Yasumoto; Katsuhiro Konno. 2019. "Comprehensive analysis of peptides and low molecular weight components of the giant ant Dinoponera quadriceps venom." Biological Chemistry , no. : 1.
SummaryThis study aimed to investigate the ability of disulphide-less crotamine (dLCr) to complex DNA and to evaluate whether the DNA–dLCr complex is capable of improving transfection in bovine embryos. Three experiments were performed to: (i) evaluate the formation and stability of the DNA–dLCr complex; (ii) assess the dLCr embryotoxicity by exposure of bovine embryos to dLCr; and (iii) assess the efficiency of bovine embryo transfection after microinjection of the DNA–dLCr complex or green fluorescent protein (GFP) plasmid alone (control). DNA complexation by dLCr after 30 min of incubation at 1:100 and 1:50 proportions presented higher efficiency (P < 0.05) than the two controls: native crotamine (NCr) 1:10 and lipofectamine. There was no difference between DNA–dLCr 1:25 and the controls. The DNA–dLCr complexation was evaluated at different proportions and times. In all, at least half of maximum complexation was achieved within the initial 30 min. No embryotoxicity of dLCr was verified after exposure of in vitro fertilized embryos to different concentrations of the peptide. The effectiveness of dLCr to improve exogenous gene expression was evaluated by microinjection of the DNA–dLCr complex into in vitro fertilized zygotes, followed by verification of both embryo development and GFP expression. From embryos microinjected with DNA only, 4.6% and 2.8% expressed the GFP transgene at day 5 and day 7, respectively. The DNA–dLCr complex did not increase the number of GFP-positive embryos. In conclusion, dLCr forms a complex with DNA and its application in in vitro culture is possible. However, the dLCr peptide sequence should be redesigned to improve GFP expression.
Vicente J.F. Freitas; Iana S. Campelo; Mirelly M.A.S. Silva; Camila M. Cavalcanti; Dárcio I.A. Teixeira; Luiz S.A. Camargo; Luciana M. Melo; Gandhi Rádis-Baptista. Disulphide-less crotamine is effective for formation of DNA–peptide complex but is unable to improve bovine embryo transfection. Zygote 2019, 28, 72 -79.
AMA StyleVicente J.F. Freitas, Iana S. Campelo, Mirelly M.A.S. Silva, Camila M. Cavalcanti, Dárcio I.A. Teixeira, Luiz S.A. Camargo, Luciana M. Melo, Gandhi Rádis-Baptista. Disulphide-less crotamine is effective for formation of DNA–peptide complex but is unable to improve bovine embryo transfection. Zygote. 2019; 28 (1):72-79.
Chicago/Turabian StyleVicente J.F. Freitas; Iana S. Campelo; Mirelly M.A.S. Silva; Camila M. Cavalcanti; Dárcio I.A. Teixeira; Luiz S.A. Camargo; Luciana M. Melo; Gandhi Rádis-Baptista. 2019. "Disulphide-less crotamine is effective for formation of DNA–peptide complex but is unable to improve bovine embryo transfection." Zygote 28, no. 1: 72-79.
Aims Crotalicidin (Ctn), a cathelicidin‐related antimicrobial peptide from the South American rattlesnake venom gland, and its C‐terminal Ctn[15‐34] fragment, have shown important activities against microorganisms, trypanosomatid protozoa and certain lines of tumor cells. Herein, the activity against clinical strains of fluconazole‐resistant Candida albicans and of amphotericin B and fluconazole‐resistant Cryptococcus neoformans was investigated. Methods and Results Microdilution and luminescent cell viability tests were used to evaluate and compare the susceptibility of pathogenic yeasts to these peptides. The time‐kill curves of the most active Ctn[15‐34] alone or in combination with fluconazole against drug‐resistant yeasts were determined. Concomitantly, the fungicidal and/or fungistatic effects of Ctn[15‐34] were visualized by the spotting test. The peptides were active against all strains, including those resistant to antifungals. The association of fluconazole with both Ctn and Ctn[15‐34], although not synergic, was additive. In contrast, such pattern was not observed for C. neoformans. Conclusions Overall, Ctn and Ctn[15‐34] are potential antifungal leads displaying anti‐yeast activities against clinical isolates endowed with drug resistance mechanisms. Significance and impact of the study The effective peptide activity against resistant strains of pathogenic yeasts demonstrates that crotalicidin‐derived peptides are promising templates to develop new antifungal pharmaceuticals.
Lidiane Aguiar; Carolina Sidrim De Paula Cavalcante; Raquel Oliveira Dos Santos Fontenelle; Cláudio Borges Falcão; David Andreu; Gandhi Rádis‐Baptista. The antiproliferative peptide Ctn[15‐34] is active against multidrug‐resistant yeasts Candida albicans and Cryptococcus neoformans. Journal of Applied Microbiology 2019, 128, 414 -425.
AMA StyleLidiane Aguiar, Carolina Sidrim De Paula Cavalcante, Raquel Oliveira Dos Santos Fontenelle, Cláudio Borges Falcão, David Andreu, Gandhi Rádis‐Baptista. The antiproliferative peptide Ctn[15‐34] is active against multidrug‐resistant yeasts Candida albicans and Cryptococcus neoformans. Journal of Applied Microbiology. 2019; 128 (2):414-425.
Chicago/Turabian StyleLidiane Aguiar; Carolina Sidrim De Paula Cavalcante; Raquel Oliveira Dos Santos Fontenelle; Cláudio Borges Falcão; David Andreu; Gandhi Rádis‐Baptista. 2019. "The antiproliferative peptide Ctn[15‐34] is active against multidrug‐resistant yeasts Candida albicans and Cryptococcus neoformans." Journal of Applied Microbiology 128, no. 2: 414-425.
Ant species have specialized venom systems developed to sting and inoculate a biological cocktail of organic compounds, including peptide and polypeptide toxins, for the purpose of predation and defense. The genus Dinoponera comprises predatory giant ants that inoculate venom capable of causing long-lasting local pain, involuntary shaking, lymphadenopathy, and cardiac arrhythmias, among other symptoms. To deepen our knowledge about venom composition with regard to protein toxins and their roles in the chemical–ecological relationship and human health, we performed a bottom-up proteomics analysis of the crude venom of the giant ant D. quadriceps, popularly known as the “false” tocandiras. For this purpose, we used two different analytical approaches: (i) gel-based proteomics approach, wherein the crude venom was resolved by denaturing sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and all protein bands were excised for analysis; (ii) solution-based proteomics approach, wherein the crude venom protein components were directly fragmented into tryptic peptides in solution for analysis. The proteomic data that resulted from these two methodologies were compared against a previously annotated transcriptomic database of D. quadriceps, and subsequently, a homology search was performed for all identified transcript products. The gel-based proteomics approach unequivocally identified nine toxins of high molecular mass in the venom, as for example, enzymes [hyaluronidase, phospholipase A1, dipeptidyl peptidase and glucose dehydrogenase/flavin adenine dinucleotide (FAD) quinone] and diverse venom allergens (homologous of the red fire ant Selenopsis invicta) and venom-related proteins (major royal jelly-like). Moreover, the solution-based proteomics revealed and confirmed the presence of several hydrolases, oxidoreductases, proteases, Kunitz-like polypeptides, and the less abundant inhibitor cysteine knot (ICK)-like (knottin) neurotoxins and insect defensin. Our results showed that the major components of the D. quadriceps venom are toxins that are highly likely to damage cell membranes and tissue, to cause neurotoxicity, and to induce allergic reactions, thus, expanding the knowledge about D. quadriceps venom composition and its potential biological effects on prey and victims.
Douglas Oscar Ceolin Mariano; Úrsula Castro De Oliveira; André Junqueira Zaharenko; Daniel Carvalho Pimenta; Gandhi Rádis-Baptista; Álvaro Rossan De Brandão Prieto-Da-Silva. Bottom-Up Proteomic Analysis of Polypeptide Venom Components of the Giant Ant Dinoponera Quadriceps. Toxins 2019, 11, 448 .
AMA StyleDouglas Oscar Ceolin Mariano, Úrsula Castro De Oliveira, André Junqueira Zaharenko, Daniel Carvalho Pimenta, Gandhi Rádis-Baptista, Álvaro Rossan De Brandão Prieto-Da-Silva. Bottom-Up Proteomic Analysis of Polypeptide Venom Components of the Giant Ant Dinoponera Quadriceps. Toxins. 2019; 11 (8):448.
Chicago/Turabian StyleDouglas Oscar Ceolin Mariano; Úrsula Castro De Oliveira; André Junqueira Zaharenko; Daniel Carvalho Pimenta; Gandhi Rádis-Baptista; Álvaro Rossan De Brandão Prieto-Da-Silva. 2019. "Bottom-Up Proteomic Analysis of Polypeptide Venom Components of the Giant Ant Dinoponera Quadriceps." Toxins 11, no. 8: 448.
Venoms from marine animals have been recognized as a new emerging source of peptide-based therapeutics. Several peptide toxins from sea anemone have been investigated as therapeutic leads or pharmacological tools. Venom complexity should be further highlighted using combined strategies of large-scale sequencing and data analysis which integrated transcriptomics and proteomics to elucidate new proteins or peptides to be compared among species. In this work, transcriptomic and proteomic analyses were combined to identify six groups of expressed peptide toxins in Zoanthus natalensis. These include neurotoxin, hemostatic and hemorrhagic toxin, protease inhibitor, mixed function enzymes, venom auxiliary proteins, allergen peptides, and peptides related to the innate immunity. Molecular docking analysis indicated that one expressed Zoanthus Kunitz-like peptide, ZoaKuz1, could be a voltage-gated potassium channels blocker and, hence, it was selected for functional studies. Functional bioassays revealed that ZoaKuz1 has an intrinsic neuroprotective activity in zebrafish model of Parkinson’s disease. Since pharmacological blockade of KV channels is known to induce neuroprotective effects, ZoaKuz1 holds the potential to be developed in a therapeutic tool to control neural dysfunction by slowing or even halting neurodegeneration mediated by ion-channel hyperactivity.
Qiwen Liao; Guiyi Gong; Terence C. W. Poon; Irene L. Ang; Kate M. K. Lei; Shirley Weng In Siu; Clarence Tsun Ting Wong; Gandhi Rádis-Baptista; Simon Ming-Yuen Lee. Combined transcriptomic and proteomic analysis reveals a diversity of venom-related and toxin-like peptides expressed in the mat anemone Zoanthus natalensis (Cnidaria, Hexacorallia). Archives of Toxicology 2019, 93, 1745 -1767.
AMA StyleQiwen Liao, Guiyi Gong, Terence C. W. Poon, Irene L. Ang, Kate M. K. Lei, Shirley Weng In Siu, Clarence Tsun Ting Wong, Gandhi Rádis-Baptista, Simon Ming-Yuen Lee. Combined transcriptomic and proteomic analysis reveals a diversity of venom-related and toxin-like peptides expressed in the mat anemone Zoanthus natalensis (Cnidaria, Hexacorallia). Archives of Toxicology. 2019; 93 (6):1745-1767.
Chicago/Turabian StyleQiwen Liao; Guiyi Gong; Terence C. W. Poon; Irene L. Ang; Kate M. K. Lei; Shirley Weng In Siu; Clarence Tsun Ting Wong; Gandhi Rádis-Baptista; Simon Ming-Yuen Lee. 2019. "Combined transcriptomic and proteomic analysis reveals a diversity of venom-related and toxin-like peptides expressed in the mat anemone Zoanthus natalensis (Cnidaria, Hexacorallia)." Archives of Toxicology 93, no. 6: 1745-1767.
We previously reported a novel toxic peptide identified from the anthozoan Protopalythoa variabilis transcriptome which is homologous to a novel structural type of sodium channel toxin isolated from a parental species (Palythoa caribaeorum). The peptide was named, according to its homologous, as Pp V-shape α-helical peptide (PpVα) in the present study. Through molecular docking and dynamics simulation, linear and hairpin folded PpVα peptides were shown to be potential voltage-gated sodium channel blockers. Nowadays, sodium channel blockers have been the mainstream of the pharmacological management of epileptic seizures. Also, sodium channel blockers could promote neuronal survival by reducing sodium influx and reducing the likelihood of calcium importation resulting in suppressing microglial activation and protecting dopaminergic neurons from degeneration. The folded PpVα peptide could decrease pentylenetetrazol (PTZ)-induced c-fos and npas4a expression level leading to reverse PTZ-induced locomotor hyperactivity in zebrafish model. In vitro, the folded PpVα peptide protected PC12 cells against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity via activating heme oxygenase-1 (HO-1) and attenuating inducible nitric oxide synthase (iNOS) expression. In vivo, PpVα peptide suppressed the 6-OHDA-induced neurotoxicity on the locomotive behavior of zebrafish and, importantly, prevented the 6-OHDA-induced excessive ROS generation and subsequent dopaminergic neurons loss. This study indicates that the single S–S bond folded PpVα peptide arises as a new structural template to develop sodium channel blockers and provides an insight on the peptide discovery from cnidarian transcriptome to potentially manage epilepsy and neurodegenerative disorders.
Qiwen Liao; Shengnan Li; Shirley Weng In Siu; Jean-Étienne R. L. Morlighem; Clarence Tsun Ting Wong; Xiufen Wang; Gandhi Rádis-Baptista; Simon Ming-Yuen Lee. Novel neurotoxic peptides from Protopalythoa variabilis virtually interact with voltage-gated sodium channel and display anti-epilepsy and neuroprotective activities in zebrafish. Archives of Toxicology 2018, 93, 189 -206.
AMA StyleQiwen Liao, Shengnan Li, Shirley Weng In Siu, Jean-Étienne R. L. Morlighem, Clarence Tsun Ting Wong, Xiufen Wang, Gandhi Rádis-Baptista, Simon Ming-Yuen Lee. Novel neurotoxic peptides from Protopalythoa variabilis virtually interact with voltage-gated sodium channel and display anti-epilepsy and neuroprotective activities in zebrafish. Archives of Toxicology. 2018; 93 (1):189-206.
Chicago/Turabian StyleQiwen Liao; Shengnan Li; Shirley Weng In Siu; Jean-Étienne R. L. Morlighem; Clarence Tsun Ting Wong; Xiufen Wang; Gandhi Rádis-Baptista; Simon Ming-Yuen Lee. 2018. "Novel neurotoxic peptides from Protopalythoa variabilis virtually interact with voltage-gated sodium channel and display anti-epilepsy and neuroprotective activities in zebrafish." Archives of Toxicology 93, no. 1: 189-206.
Marine invertebrates, such as sponges, tunicates and cnidarians (zoantharians and scleractinian corals), form functional assemblages, known as holobionts, with numerous microbes. This type of species-specific symbiotic association can be a repository of myriad valuable low molecular weight organic compounds, bioactive peptides and enzymes. The zoantharian Protopalythoa variabilis (Cnidaria: Anthozoa) is one such example of a marine holobiont that inhabits the coastal reefs of the tropical Atlantic coast and is an interesting source of secondary metabolites and biologically active polypeptides. In the present study, we analyzed the entire holo-transcriptome of P. variabilis, looking for enzyme precursors expressed in the zoantharian-microbiota assemblage that are potentially useful as industrial biocatalysts and biopharmaceuticals. In addition to hundreds of predicted enzymes that fit into the classes of hydrolases, oxidoreductases and transferases that were found, novel enzyme precursors with multiple activities in single structures and enzymes with incomplete Enzyme Commission numbers were revealed. Our results indicated the predictive expression of thirteen multifunctional enzymes and 694 enzyme sequences with partially characterized activities, distributed in 23 sub-subclasses. These predicted enzyme structures and activities can prospectively be harnessed for applications in diverse areas of industrial and pharmaceutical biotechnology.
Jean-Étienne R. L. Morlighem; Chen Huang; Qiwen Liao; Paula Braga Gomes; Carlos Daniel Pérez; Álvaro Rossan De Brandão Prieto-Da-Silva; Simon Ming-Yuen Lee; Gandhi Rádis-Baptista; Álvaro De Brandão Prieto-Da-Silva. The Holo-Transcriptome of the Zoantharian Protopalythoa variabilis (Cnidaria: Anthozoa): A Plentiful Source of Enzymes for Potential Application in Green Chemistry, Industrial and Pharmaceutical Biotechnology. Marine Drugs 2018, 16, 207 .
AMA StyleJean-Étienne R. L. Morlighem, Chen Huang, Qiwen Liao, Paula Braga Gomes, Carlos Daniel Pérez, Álvaro Rossan De Brandão Prieto-Da-Silva, Simon Ming-Yuen Lee, Gandhi Rádis-Baptista, Álvaro De Brandão Prieto-Da-Silva. The Holo-Transcriptome of the Zoantharian Protopalythoa variabilis (Cnidaria: Anthozoa): A Plentiful Source of Enzymes for Potential Application in Green Chemistry, Industrial and Pharmaceutical Biotechnology. Marine Drugs. 2018; 16 (6):207.
Chicago/Turabian StyleJean-Étienne R. L. Morlighem; Chen Huang; Qiwen Liao; Paula Braga Gomes; Carlos Daniel Pérez; Álvaro Rossan De Brandão Prieto-Da-Silva; Simon Ming-Yuen Lee; Gandhi Rádis-Baptista; Álvaro De Brandão Prieto-Da-Silva. 2018. "The Holo-Transcriptome of the Zoantharian Protopalythoa variabilis (Cnidaria: Anthozoa): A Plentiful Source of Enzymes for Potential Application in Green Chemistry, Industrial and Pharmaceutical Biotechnology." Marine Drugs 16, no. 6: 207.
Palythoa caribaeorum (class Anthozoa) is a zoantharian which, together with other cnidarians, like jellyfishes, hydra, and sea anemones, possesses specialized structures in its tissues, the cnidocytes, which deliver an array of toxins in order to capture prey and deter predators. The whole transcriptome of P. caribaeroum was deep sequenced, and a diversity of toxin-related peptide sequences were identified, and some retrieved for functional analysis. In this work, a peptide precursor containing a ShK domain, named PcShK3, was analyzed by means of computational processing, comprising structural phylogenetic analysis, model prediction, and dynamics simulation of peptide-receptor interaction. The combined data indicated that PcShK3 is a distinct peptide which is homologous to a cluster of peptides belonging to the ShK toxin family. In vivo, PcShK3 distributed across the vitelline membrane and accumulated in the yolk sac stripe of zebrafish larvae. Notably, it displayed a significant cardio-protective effect in zebrafish in concentrations inferior to the IC50 (IC50), it accumulated in the blood and caused pericardial edema, being cardiotoxic to zebrafish larvae. Remarkably, PcShK3 suppressed the 6-OHDA-induced neurotoxicity on the locomotive behavior of zebrafish. The present results indicated that PcShK3 is a novel member of ShK toxin family, and has the intrinsic ability to induce neuro- and cardio-protective effects or cause cardiac toxicity, according to its effective concentration.
Qiwen Liao; Guiyi Gong; Shirley Weng In Siu; Clarence Tsun Ting Wong; Huidong Yu; Yu Chung Tse; Gandhi Rádis-Baptista; Simon Ming-Yuen Lee. A Novel ShK-Like Toxic Peptide from the Transcriptome of the Cnidarian Palythoa caribaeorum Displays Neuroprotection and Cardioprotection in Zebrafish. Toxins 2018, 10, 238 .
AMA StyleQiwen Liao, Guiyi Gong, Shirley Weng In Siu, Clarence Tsun Ting Wong, Huidong Yu, Yu Chung Tse, Gandhi Rádis-Baptista, Simon Ming-Yuen Lee. A Novel ShK-Like Toxic Peptide from the Transcriptome of the Cnidarian Palythoa caribaeorum Displays Neuroprotection and Cardioprotection in Zebrafish. Toxins. 2018; 10 (6):238.
Chicago/Turabian StyleQiwen Liao; Guiyi Gong; Shirley Weng In Siu; Clarence Tsun Ting Wong; Huidong Yu; Yu Chung Tse; Gandhi Rádis-Baptista; Simon Ming-Yuen Lee. 2018. "A Novel ShK-Like Toxic Peptide from the Transcriptome of the Cnidarian Palythoa caribaeorum Displays Neuroprotection and Cardioprotection in Zebrafish." Toxins 10, no. 6: 238.
Crotalicidin (Ctn), a cathelicidin-related peptide from the venom of a South American rattlesnake, possesses potent antimicrobial, antitumor, and antifungal properties. Previously, we have shown that its C-terminal fragment, Ctn(15–34), retains the antimicrobial and antitumor activities but is less toxic to healthy cells and has improved serum stability. Here, we investigated the mechanisms of action of Ctn and Ctn(15–34) against Gram-negative bacteria. Both peptides were bactericidal, killing ∼90% of Escherichia coli and Pseudomonas aeruginosa cells within 90–120 and 5–30 min, respectively. Studies of ζ potential at the bacterial cell membrane suggested that both peptides accumulate at and neutralize negative charges on the bacterial surface. Flow cytometry experiments confirmed that both peptides permeabilize the bacterial cell membrane but suggested slightly different mechanisms of action. Ctn(15–34) permeabilized the membrane immediately upon addition to the cells, whereas Ctn had a lag phase before inducing membrane damage and exhibited more complex cell-killing activity, probably because of two different modes of membrane permeabilization. Using surface plasmon resonance and leakage assays with model vesicles, we confirmed that Ctn(15–34) binds to and disrupts lipid membranes and also observed that Ctn(15–34) has a preference for vesicles that mimic bacterial or tumor cell membranes. Atomic force microscopy visualized the effect of these peptides on bacterial cells, and confocal microscopy confirmed their localization on the bacterial surface. Our studies shed light onto the antimicrobial mechanisms of Ctn and Ctn(15–34), suggesting Ctn(15–34) as a promising lead for development as an antibacterial/antitumor agent.
Clara Pérez-Peinado; Susana Dias; Marco Domingues; Aurélie Benfield; João Miguel Freire; Gandhi Rádis-Baptista; Diana Gaspar; Miguel Castanho; David J. Craik; Sónia Troeira Henriques; Ana Salomé Veiga; David Andreu. Mechanisms of bacterial membrane permeabilization by crotalicidin (Ctn) and its fragment Ctn(15–34), antimicrobial peptides from rattlesnake venom. Journal of Biological Chemistry 2018, 293, 1536 -1549.
AMA StyleClara Pérez-Peinado, Susana Dias, Marco Domingues, Aurélie Benfield, João Miguel Freire, Gandhi Rádis-Baptista, Diana Gaspar, Miguel Castanho, David J. Craik, Sónia Troeira Henriques, Ana Salomé Veiga, David Andreu. Mechanisms of bacterial membrane permeabilization by crotalicidin (Ctn) and its fragment Ctn(15–34), antimicrobial peptides from rattlesnake venom. Journal of Biological Chemistry. 2018; 293 (5):1536-1549.
Chicago/Turabian StyleClara Pérez-Peinado; Susana Dias; Marco Domingues; Aurélie Benfield; João Miguel Freire; Gandhi Rádis-Baptista; Diana Gaspar; Miguel Castanho; David J. Craik; Sónia Troeira Henriques; Ana Salomé Veiga; David Andreu. 2018. "Mechanisms of bacterial membrane permeabilization by crotalicidin (Ctn) and its fragment Ctn(15–34), antimicrobial peptides from rattlesnake venom." Journal of Biological Chemistry 293, no. 5: 1536-1549.