CRAMP analog having potent antibiotic activity without hemolytic activity.
CRAMP-18 is an 18-residue functional region, corresponding to residues 16-33 of a mouse-derived antibiotic peptide CRAMP. To develop novel antibiotic peptides possessing strong antibiotic activity against bacterial, fungal and tumor cells without hemolytic activity, three analogs of CRAMP-18 were synthesized containing either Leu- or Lys-substitution. Leu-substitution ([L(1, 8)]-CRAMP-18) in the hydrophobic helix face of CRAMP-18 induced a dramatic increase in antibiotic activity without a significant increase in hemolytic activity. Lys-substitution ([K(2, 13)]-CRAMP-18 or [K(9, 16)]-CRAMP-18) in the hydrophilic helix face produced a smaller response. Therefore, [L(1, 8)]-CRAMP-18 may be an attractive candidate for developing novel peptide antibiotics.
Kang
Shin-Won
SW
Department of Chemistry, Pusan National University, Pusan, 609-735, Korea.
Lee
Dong Gun
DG
Yang
Sung-Tae
ST
Kim
Yangmee
Y
Kim
Jae Il
JI
Hahm
Kyung-Soo
KS
Shin
Song Yub
SY
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001232:Aspergillus fumigatus / Q000187:drug effects; D001419:Bacteria / Q000187:drug effects; D054804:Cathelicidins; D002942:Circular Dichroism; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D014407:Tumor Cells, Cultured
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; D054804:Cathelicidins; D010455:Peptides; D011506:Proteins