Antimicrobial peptides (AMPs) are a diverse group of small, naturally occurring molecules that orchestrate the innate immune response of various organisms, from microorganisms to humans. Characterized by their broad-spectrum activity against bacteria, fungi and viruses, AMPs are increasingly recognized for their potential as novel therapeutic agents in the face of rising antibiotic resistance. Here, we present several newly designed AMPs, one of which, DTN6, exerts significant activity against several organisms with MIC values as low as 0.5 µg/mL. The D-TN6 peptide influences both bacteria and yeasts. Scanning electron microscopy and transmission electron microscopy results showed that the bacterial membrane is affected by D-TN6, which is resistant to proteases and is effective against antibiotic-resistant pathogens with hemolytic activity and low toxicity. The D-TN6 peptide is effective in vivo against standard S. aureus strains in wounds. Thus, D-TN6 is a potent antibiotic candidate with a broad spectrum of activity. Overall, AMPs are a promising tool for the development of next-generation antimicrobial agents that could mitigate global health threats posed by multidrug-resistant pathogens.

Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine associated with TNF receptor 1 (TNFR1) and TNF receptor 2 (TNFR2), which play important roles in several inflammatory diseases. There is a growing interest in developing alternative molecules that can be used as TNF blockers. In this study, we focused on TNF-α-, TNFR1-, and TNFR2-mimicking peptides to inhibit TNF-α receptor binding in various ways. Six peptides (OB1, OB2, OB5, OB6, OB7, and OB8) were developed to bind TNFR1, TNFR2, and TNF-α. OB1 and OB2 bound to TNF-α with lower K_d values of 300 and 46.7 nM, respectively, compared to previously published sequences. These synthetic peptides directly and indirectly inhibited TNF-α in vitro without cytotoxicity to L929 cells, and OB1 significantly inhibited apoptosis in the presence of hTNF-α. Peptides developed in this study may prove to be useful for therapeutic inhibition of TNF-α.

Polymer coatings as thin films stand out as a commonly used strategy to modify biosensor surfaces for improving detection performance; however, nonspecific biomolecule interactions and the limited degree of ligand conjugation on the surface have necessitated the development of innovative methods for surface modification. To this end, methacrylated tethered telechelic polyethylene glycol (PEG-diMA) chains of three different molecular weights (2, 6, and 10 kDa) were synthesized herein and used for obtaining thiolated nanoparticles (NPs) upon adding excess amounts of a tetra-thiol crosslinker. Characterized according to their size, surface charge, morphology, and thiol amounts, these nanoparticles were immobilized on gold surfaces that mimicked gold-coated mass sensor platforms. The PEG-based nanoparticles, prepared especially by PEG6K-diMA polymers, were shown to result in the preparation of a monolayer and smooth coating of 80–120 nm thickness. Cysteine-modified NTS(8–13) peptide (RRPYIL) was conjugated to thiolated NP with reversible disulfide bonds and it was demonstrated that its cleavage with a reducing agent such as dithiothreitol (DTT) restores the NP-immobilized gold surface for at least two cycles. Together with its binding studies to NTSR2 antibodies, it was revealed that the peptide-conjugated NP-modified gold surface could be employed as a model for a reusable sensor surface for the detection of biomarkers of same or different types.

Background/Objectives: The growing threat of antibiotic resistance necessitates the development of novel antimicrobial agents that effectively target pathogenic microorganisms while minimizing toxicity. Methods: Two series DABCO-based cationic homopolymers (D-subs 1kDa, D-subs 5kDa, D-subs 15kDa) and DABCO–pyridinium-based copolymers (PyH-subs 5kDa_Dsubs 5kDa, PyH-subs 7kDa_Dsubs 3kDa, PyH-subs 3kDa_Dsubs 7kDa) were synthesized to mimic to host-defense cationic peptides via ring-opening metathesis polymerization (ROMP). The antimicrobial activities of these polymers were determined by their minimum inhibitory concentrations (MICs) against E. coli (Gram-negative bacteria), P. aeruginosa (Gram-negative bacteria), S. aureus (Gram-positive bacteria), and C. albicans (fungus). In vitro cytotoxicity assays revealed selective toxicity towards bacterial cells, with high selectivity indices for several copolymers. To gain insight into the mechanism of action, morphological changes in S. aureus upon exposure to D-subs 1kDa were examined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Results: The D-subs 15kDa homopolymer demonstrated the highest overall antimicrobial activity, particularly against S. aureus (MIC: 8 µg/mL), with all polymers exhibiting minimal hemolytic activity (HC₅₀ ≥ 1024 µg/mL). SEM and TEM results revealed membrane disruption indicative of polymer–bacteria interactions. Additionally, stability studies confirmed polymer integrity under physiological conditions for at least 28 days. Conclusions: These results support the potential of DABCO-based cationic polymers as a promising platform for next-generation antimicrobial therapeutics.

Objectives: The escalation of multidrug-resistant (MDR) clinically relevant bacterial isolates, including Escherichia coli and key ESKAPE pathogens, represents a critical global healthcare threat. While antimicrobial peptides (AMPs) offer promising alternatives, metabolic instability often limits their clinical use. This study investigated the therapeutic potential, antimicrobial efficacy, and resistance dynamics of peptide D-TN6 against highly resistant bacterial strains. Methods: D-TN6 efficacy was evaluated against 164 clinical isolates, including pan-drug-resistant, carbapenem-resistant, and polymyxin-resistant phenotypes. A 20-passage serial induction assay compared resistance development kinetics of D-TN6 against gentamicin over an extended period. Results: D-TN6 demonstrated potent efficacy against MRSA (minimum inhibitory concentration (MIC)₉₀: 1 µg/mL) and remained effective against polymyxin B-resistant Klebsiella pneumoniae (MIC₉₀: 8 µg/mL) and pan-drug-resistant Acinetobacter baumannii (MIC₉₀: 8 µg/mL). In resistance assays, while the gentamicin MIC increased 256-fold by the 17th passage, the D-TN6 MIC remained constant at 1 µg/mL throughout the 20-passage study. Conclusions: These findings underscore D-TN6 as a robust therapeutic candidate. Its efficacy against MDR strains and its feature of low propensity for resistance development—likely due to membrane disruption—position D-TN6 as a promising solution for life-threatening infections where conventional last-resort agents fail.