Mitsuno Shindo

Structure‐activity relationship of indolicidin, a Trp‐rich antibacterial peptide

A series of Trp and Arg analogs of antibacterial indolicidin (Ind) was synthesized and the antimicrobial and hemolytic activities were investigated. [L9]Ind, [L11]Ind, [K8,L9]Ind and [K6, 8,L9]Ind showed desirable characteristics, exhibiting negligible hemolytic activity while keeping strong antibacterial activity. The results indicated that the Trp residue at position 11 essentially contributes to both activities and one can not be exchanged for the other, whereas the Trp residues at positions 4 and 9 play important roles in antimicrobial and hemolytic activities, respectively. The Trp residues at positions 6 and 8 play no important roles in biological activities. We then found that the retro analog of Ind showed higher antibacterial activity than Ind against both Gram‐positive and Gram‐negative bacteria but remarkably lower hemolytic activity than that of Ind. Copyright

A Novel, Antimicrobially Active Analog of Gramicidin S without Amphiphilic Conformation

A novel gramicidin S analog, cyclo(-Val-Leu-Leu-Orn-Leu-D-Phe-Pro-)2, was synthesized, its antibiotic activity compared with gramicidin S and shown to be as potent as gramicidin S when compared with the susceptibility toward five Gram-positive microorganisms. It exceeded the activity of gramicidin S against Bacillus megaterium ATCC 19213 by a factor of two. Circular dichroism and NMR data suggested this analog to adopt an antiparallel β-sheet conformation without amphiphilic character.

Design and syntheses of gramicidin S analogs, cyclo(-X-Leu-X-D-Phe-Pro-) 2 (X=His, Lys, Orn, Dab and Dap)

Design and syntheses of gramicidin S analogs, cyclo(-X-Leu-X-D-Phe-Pro-) 2 (X=His, Lys, Orn, Dab and Dap)

A novel polycationic analogue of gratisin with antibiotic activity against both Gram-positive and Gram-negative bacteria.

AbstractA novel polycationic analogue of gratisin, cyclo(-Val-Orn-Leu-D-Phe-Pro-D-Lys-)2, was designed and synthesized, which exhibited strong activity against all Gram-positive and Gram-negative bacteria tested. Its activity against Pseudomonas aeruginosa IFO 3080 was two times higher than gramicidin S.