Peptide-based subunit vaccines are of great interest in modern immunotherapy as they are safe, easy to produce and well defined. However, peptide antigens produce a relatively weak immune response, and thus require the use of immunostimulants (adjuvants) for optimal efficacy. Developing a safe and effective adjuvant remains a challenge for peptide-based vaccine design. Recent advances in immunology have allowed researchers to have a better understanding of the immunological implication of related diseases, which facilitates more rational design of adjuvant systems. Understanding the molecular structure of the adjuvants allows the establishment of their structure-activity relationships which is useful for the development of next-generation adjuvants. This review summarizes the current state of adjuvants development in the field of synthetic peptide-based vaccines. The structural, chemical and biological properties of adjuvants associated with their immunomodulatory effects are discussed.
The copper (I)-catalyzed alkyne azide 1,3-dipolar cycloaddition (CuAAC) or ‘click’ reaction, is a highly versatile reaction that can be performed under a variety of reaction conditions including various solvents, a wide pH and temperature range, and using different copper sources, with or without additional ligands or reducing agents. This reaction is highly selective and can be performed in the presence of other functional moieties. The flexibility and selectivity has resulted in growing interest in the application of CuAAC in various fields. In this review, we briefly describe the importance of the structural folding of peptides and proteins and how the 1,4-disubstituted triazole product of the CuAAC reaction is a suitable isoster for an amide bond. However the major focus of the review is the application of this reaction to produce peptide conjugates for tagging and targeting purpose, linkers for multifunctional biomacromolecules, and reporter ions for peptide and protein analysis.
To fulfil the growing needs of the global population, sustainability in food production must be ensured. Insect pests and pathogens are primarily responsible for one-third of food losses and harmful synthetic pesticides have been applied to protect crops from these pests and other pathogens such as viruses and fungi. An alternative pathogen control mechanism that is more “friendly” to the environment can be developed by externally applying double-stranded RNAs (dsRNAs) to suppress gene expression. However, the use of dsRNA sprays in open fields is complicated with respect to variable efficiencies in the dsRNA delivery, and the stability of the dsRNA on and in the plants, and because the mechanisms of gene silencing may differ between plants and between different pathogen targets. Thus, nanocarrier delivery systems have been especially used with the goal of improving the efficacy of dsRNAs. Here, we highlight recent developments in nanoparticle-mediated nanocarriers to deliver dsRNA, including layered double hydroxide, carbon dots, carbon nanotubes, gold nanoparticles, chitosan nanoparticles, silica nanoparticles, liposomes, and cell-penetrating peptides, by review of the literature and patent landscape. The effects of nanoparticle size and surface modification on the dsRNA uptake efficiency in plants are also discussed. Finally, we emphasize the overall limitation of dsRNA sprays, the risks associated, and the potential safety concerns for spraying dsRNAs on crops.
1 November 2014 in Bioorganic & Medicinal Chemistry
To explore four-arm star poly(t-butyl)acrylate (P(t)BA)-peptide and linear P(t)BA-peptide conjugates as a vaccine-delivery system against Group A Streptococcus. P(t)BA nanoparticles bearing J14 peptide epitopes were prepared via alkyne-azide 1,3-dipolar cycloaddition 'click' reaction. The conjugated products were self-assembled into small or large nanoparticles. These nanoparticle vaccine candidates were evaluated in vivo and J14-specific antibody titers were assessed. Mice vaccinated with the nanoparticles were able to produce J14-specific IgG antibodies without the use of an external adjuvant after a single immunization. We have demonstrated for the first time that the immune responses against self-assembled P(t)BA nanoparticles are stronger for the smaller sized (~20 nm) nanoparticles compared with the larger (~500 nm) P(t)BA nanoparticles. PtBA analogs have the potential to be developed as potent carrier systems for single-dose synthetic vaccines.