Generating\na Peptide Library Using the Repeats of\nAmino Acid Scaffolds Created by Sliding the Framework of a 7‑mer\nHuman Chemerin Segment and Discovery of Potent Antibacterial and Antimycobacterial\nPeptides

The quest for new approaches for generating novel bioactive\ndesigner\nproteins/peptides has continued with their success in various biomedical\napplications. Previously, we designed a 14-mer α-helical peptide\nwith antimicrobial and antimycobacterial activities by employing a\ntandem repeat of the 7-mer, “KVLGRLV” human chemerin\nsegment. Herein, we devised a new method of “sliding framework”\nwith this segment to create amino acid scaffolds of varying sizes\nand sequences and explored the design of a peptide library with antibacterial\nand antimycobacterial activities. By utilizing 2 to 7 repeats of these\n2 to 6-residue scaffolds, we designed and synthesized 30 peptides\nof 10–16 residue lengths. Thus, we identified novel AMPs with\nα-helical, β-sheet, and random coil structures, membrane-destabilizing,\nand intracellular modes of action, and 9 of them showed therapeutic\nindices between 100 and 750. Three and two of these nine peptides\nshowed <i>in vivo</i> antibacterial and antitubercular efficacies\nagainst Escherichia coli ATCC 25922\nand Mycobacterium bovis BCG infections,\nrespectively, in a mouse model.