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 <i>in vivo</i> antibacterial and antitubercular efficacies against <i>Escherichia coli</i> ATCC 25922 and <i>Mycobacterium bovis</i> BCG infections, respectively, in a mouse model.