Generating a Peptide Library Using the Repeats of Amino Acid Scaffolds Created by Sliding the Framework of a 7-mer Human Chemerin Segment and Discovery of Potent Antibacterial and Antimycobacterial Peptides.

The quest for new approaches for generating novel bioactive designer proteins/peptides has continued with their success in various biomedical applications. Previously, we designed a 14-mer α-helical peptide with antimicrobial and antimycobacterial activities by employing a tandem repeat of the 7-mer, "KVLGRLV" human chemerin segment. Herein, we devised a new method of "sliding framework" with this segment to create amino acid scaffolds of varying sizes and sequences and explored the design of a peptide library with antibacterial and antimycobacterial activities. By utilizing 2 to 7 repeats of these 2 to 6-residue scaffolds, we designed and synthesized 30 peptides of 10-16 residue lengths. Thus, we identified novel AMPs with α-helical, β-sheet, and random coil structures, membrane-destabilizing, and intracellular modes of action, and 9 of them showed therapeutic indices between 100 and 750. Three and two of these nine peptides showed in vivo antibacterial and antitubercular efficacies against Escherichia coli ATCC 25922 and Mycobacterium bovis BCG infections, respectively, in a mouse model.