Journal of Peptide Science最新文献

Pharmaceuticals often suffer from limitations such as low solubility, low stability, and  short half-life. To address these challenges and reduce the need for frequent drug administrations, a more efficient delivery is required. In this context, the development of controlled drug delivery systems, acting as a protective depot for the drug, has expanded significantly over the last decades. Among these, injectable hydrogels have emerged as a promising platform, especially in view of the rise of biologicals as therapeutics. Hydrogels are functional, solid-like biomaterials, composed of cross-linked hydrophilic polymers and high water content. Their physical properties, which closely mimic the extracellular matrix, make them suitable for various biomedical applications. This review discusses the different types of hydrogel systems and their self-assembly process, with an emphasis on peptide-based hydrogels. Due to their structural and functional diversity, biocompatibility, synthetic accessibility, and tunability, peptides are regarded as promising and versatile building blocks. A comprehensive overview of the variety of peptide hydrogels is outlined, with β-sheet forming sequences being highlighted. Key factors to consider when using peptide hydrogels as a controlled drug delivery system are reviewed, along with a discussion of the main drug release mechanisms and the emerging trend towards affinity-based systems to further refine drug release profiles.

Scorpion venom contains linear peptides without disulfide bonds in addition to peptides with disulfide bonds. Many such linear peptides have an amphiphilic α-helical structure, often with antimicrobial activity and can be classified into three groups based on their molecular size. Among them, long-chain antimicrobial peptides consisting of more than 40 residues have not been thoroughly studied due to the difficulty of synthesizing them. We have previously reported a transcriptome analysis of the venom gland of Liocheles australasiae that revealed precursor sequences of long-chain antimicrobial peptides. In the study reported here, we identified the mature structure of one such long-chain antimicrobial peptide, LaCT1, which we synthesized using chemical ligation to confirm its structure and evaluate its biological activities. The result showed that LaCT1 exhibited significant antimicrobial activity. In addition, we identified its partial peptides consisting of an N- or C-terminal region, which may be generated by enzymatic cleavage in the venom. Among them, only the peptide containing the N-terminal half region was active. LaCT1 also not only showed insecticidal activity but also synergistically enhanced the effects of another insecticidal peptide identified in L. australasiae venom as well. These results provide insights into the role of antimicrobial peptides in scorpion venom.

Protein–protein interactions (PPIs) have been recognized as a promising target for the development of new drugs, as proved by the growing number of PPI modulators reaching clinical trials. In this context, peptides represent a valid alternative to small molecules, owing to their unique ability to mimic the target protein structure and interact with wider surface areas. Among the possible fields of interest, bacterial PPIs represent an attractive target to face the urgent necessity to fight antibiotic resistance. Growing attention has been paid to the YgjD/YeaZ/YjeE complex responsible for the essential t⁶A₃₇ tRNA modification in bacteria. We previously identified an α-helix on the surface of Pseudomonas aeruginosa YeaZ, crucial for the YeaZ-YeaZ homodimer formation and the conserved YeaZ-YgjD interactions. Herein, we present our studies for impairing the PPIs involved in the formation of the YeaZ dimers through synthetic peptide derivatives of this helical moiety, both in vitro with purified components and on P. aeruginosa cells. Our results proved the possibility of targeting those PPIs which are usually essential for protein functioning and thus are refractory to mutational changes and antibiotic resistance development.

Chemical synthesis of complex peptides and proteins continues to play increasingly important roles in industry and academia, where strategies for covalent ligation of two or more peptide fragments to produce longer peptides and proteins in convergent manners have become critical. In recent decades, efficient and site-selective ligation strategies mediated by exploiting the biocatalytic capacity of nature's diverse toolkit (i.e., enzymes) have been widely recognized as a powerful extension of existing chemical strategies. In this review, we present a chronological overview of the development of proteases, transpeptidases, transglutaminases, and ubiquitin ligases. We survey the different properties between the ligation reactions of various enzymes, including the selectivity and efficiency of the reaction, the ligation “scar” left in the product, the type of amide bond formed (natural or isopeptide), the synthetic availability of the reactants, and whether the enzymes are orthogonal to another. This review also describes how the inherent specificity of these enzymes can be exploited for peptide and protein ligation.