Structure-activity studies of analogues of blomhotin mediating contraction of rat fundus.
Blomhotin is a novel peptide (pGlu1-Gly2-Arg3-Pro4-Pro5-Gly6-Pro7-Pro8-Ile9-Pro10-Arg11) which has been isolated from the venom of Agkistrodon halys blomhoffii and exhibits contractile activity on rat stomach fundus. We carried out a structure-activity study of blomhotin and its related peptides, and the findings suggested that the N-terminal portion of blomhotin is mainly responsible for affinity for the blomhotin receptor, whereas the C-terminal portion of blomhotin, Pro-Ile-Pro-Arg, is responsible for complete activation of the blomhotin receptor in the rat stomach fundus. In particular, the amino acids at positions 9 and 11 of blomhotin appear to be essential for binding and intrinsic activity. Using knowledge gained from this structure-activity analysis, we have identified photoactive blomhotin analogues that have sufficient biological activity to probe the target molecule of blomhotin.
Yanoshita
R
R
Institute of Medicinal Chemistry, Hoshi University, Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
Iwasaki
E
E
Kambe
T
T
Samejima
Y
Y
D000818:Animals; D003435:Crotalid Venoms / Q000819:agonists / Q000737:chemistry / Q000494:pharmacology*; D005748:Gastric Fundus / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D019920:Photoaffinity Labels; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
C031442:Agkistrodon venoms; D003435:Crotalid Venoms; D019920:Photoaffinity Labels; C420365:blomhotin; D011761:Pyrrolidonecarboxylic Acid