[Synthesis and cardioprotective properties of apelin-12 and its structural analogs].
The apelin-12 and a number of its analogs, resistant to degradation of proteases, were synthesized by Fmoc- method of SPPS. By-products of synthesis were examined. It was found that serine hydroxyl group was sulfating during the final deprotection of apelin-12 (I) and its analogs. Sulfate moiety of Arg-protecting group transfer into hydroxyl group of Ser. Amount of by-product depends on presence of water in cleavage mixture. Furthermore, the final deprotection of amide analogs of apelin-12 (III, IV) is closed with formation of by-product--4-hydroxybenzylamide, its amount range on 20-8% on reaction mixture accordance HPLC data and also depend on composition of cleavage mixture. Effects of the synthesized peptides on recovery of cardiac function after ischemia were examined in a model of isolated perfused rat heart. Infusions of any of the peptides (I-V) before ischemia resulted in a significant improvement of contractile and pump function recovery compared to the control. Cardioptotective efficacy of the peptides increased in the following rank (I) < (II) = (III) < (IV) = (V).
M V
MV
Sidorova
A A
AA
Az'muko
M E
ME
Pal'keeva
A S
AS
Molokoedov
V N
VN
Bushuev
S N
SN
Dvoriantsev
V S
VS
Shul'zhenko
V S
VS
Pelogeĭkina
O I
OI
Pisarenko
Zh D
ZhD
Bespalova
D000818:Animals; D002316:Cardiotonic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D036341:Intercellular Signaling Peptides and Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects*
D002316:Cardiotonic Agents; D036341:Intercellular Signaling Peptides and Proteins; C495200:apelin-12 peptide