LAUSR

Bovine cathelicidin, BMAP‐28 exhibits potent antimicrobial activity without any cell‐selectivity. Considering the role of its C‐terminus amino acid residues in its cytotoxic activities, we envisioned to rearrange the amino acids at its C‐terminus without altering its composition for designing new cell‐selective BMAP‐28‐analog. Thus an isoleucine residue at 20th position, also an “a” position of its previously identified isoleucine zipper sequence, was exchanged with a proline residue at 19th position. As a result, a remarkable reduction in the hemolytic activity of BMAP‐28 toward human red blood cells (hRBCs) was observed without hampering its antibacterial activity in liquid media, and in presence of salts and serum. BMAP‐28‐analog, BMAP‐28M depolarized S. aureus membrane and bacterial membrane‐mimetic, PE/PG lipid vesicles similar to BMAP‐28 but showed weaker efficacy to depolarize hRBC membrane and mammalian membrane‐mimetic, PC/Chol vesicles. Differences in the localization of tryptophan residues of BMAP‐28 and BMAP‐28M were observed only in PC/Chol vesicles. BMAP‐28 induced pores of ~3.4 nm diameter onto hRBCs whereas BMAP‐28M showed minor perturbation onto these cells. BMAP‐28 and BMAP‐28M induced the entry of calcein (size, ~1 nm) and 4.4 kDa FITC‐dextran (size, ~2.8 nm) into B. megaterium but not of higher sized fluorescent‐dextrans indicating toroidal pore formation onto these bacterial membranes.