Structure-activity analysis of SMAP-29, a sheep leukocytes-derived antimicrobial peptide.
SAMP-29 is a cathelecidin-derived antimicrobial peptide deduced from sheep myeloid mRNA. To elucidate the structural-activity relationship of SMAP-29, several analogues were synthesized and their antibiotic activity was investigated. Compared to parental SMAP-29, SMAP-29(1-17) and [K(22,25,27)]-SMAP-29 retained relatively effective antimicrobial activity (MIC: 1.0-8.0 microM), but resulted in a complete loss of hemolytic activity. Pro-19 --> Ala substitution ([A19]-SMAP-29) in SMAP-29 induced a significant reduction in antibacterial activity. These results suggested that the N-terminal amphipathic alpha-helical region and the C-terminal hydrophobic region of SMAP-29 are responsible for antimicrobial activity and hemolytic activity, respectively, and the central Pro-19 in SMAP-29 plays a critical role in showing improved antibacterial activity. In particular, [K(2,7,13)]-SMAP-29(1-17) showed potent antimicrobial activity under high salt conditions without hemolytic activity. Thus, this short peptide could serve as an attractive candidate for the development of therapeutic antimicrobial drugs. Structural analysis by circular dichroism suggested that SMAP-29 seems to adopt a helix-bend/turn-extended random conformation.
Shin
S Y
SY
Department of Life Science, Kwangju Institute of Science and Technology, Kwangju, 500-712, Korea.
Park
E J
EJ
Yang
S T
ST
Jung
H J
HJ
Eom
S H
SH
Song
W K
WK
Kim
Y
Y
Hahm
K S
KS
Kim
J I
JI
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001798:Blood Proteins / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D054804:Cathelicidins; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006460:Hemolysin Proteins / Q000494:pharmacology*; D007962:Leukocytes; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D012756:Sheep; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D001798:Blood Proteins; D054804:Cathelicidins; D006460:Hemolysin Proteins; D010446:Peptide Fragments; C403305:SMAP29 protein, Ovis aries