Structure-activity analysis of SMAP-29, a sheep leukocytes-derived antimicrobial peptide

peptide deduced from sheep myeloid mRNA. To elucidate the structural-activi ty relationship of SMAP-29, several analogues were synthesized and their an tibiotic activity was investigated. Compared to parental SMAP-29, SMAP-29(1 -17) and [K-22,K-25,K-27]-SMAP-29 retained relatively effective antimicrobi al activity (MIC: 1.0-8.0 muM), but resulted in a complete loss of hemolyti c activity. Pro-19 --> Ala substitution ([A(19)]-SMAP-29) in SMAP-29 induce d a significant reduction in antibacterial activity. These results suggeste d that the N-terminal amphipathic alpha -helical region and the C-terminal hydrophobic region of SMAP-29 are responsible for antimicrobial activity an d hemolytic activity, respectively, and the central Pro-19 in SMAP-29 plays a critical role in showing improved antibacterial activity. In particular, [K-2,K-7,K-13]-SMAP-29(1-17) showed potent antimicrobial activity under hi gh salt conditions without hemolytic activity. Thus, this short peptide cou ld serve as an attractive candidate for the development of therapeutic anti microbial drugs. Structural analysis by circular dichroism suggested that S MAP-29 seems to adopt a helix-bend/turn-extended random conformation. (C) 2 001 Academic Press.