Synthesis and cardioprotective properties of apelin-12 and its structural analogues

Autor: Yu. A. Pelogeykina, Pal'keeva Me, A. A. Az’muko, Oleg I. Pisarenko, Maria Sidorova, A. S. Molokoedov, V. N. Bushuev, Zh. D. Bespalova, Shul'zhenko Vs, S. N. Dvoryantsev
Rok vydání: 2012
Předmět:
Zdroj: Russian Journal of Bioorganic Chemistry. 38:30-40
ISSN: 1608-330X
1068-1620
DOI: 10.1134/s1068162012010177
Popis: Apelin-12 and a number of its analogues (Nle10-, MeArg1, Nle10, MeArg1, Nle10, Phe12-NH2-, Arg1(NO2), Nle10, Phe12-NH2-), resistant to the degradation of proteases, were synthesized by the Fmocmethod of SPPS. By-products of synthesis were examined. It was found that the serine hydroxyl group was sulfating during the final deprotection of apelin-12 and its analogues. The sulfate moiety of the Arg-protecting group transfers into the hydroxyl group of Ser. The amount of by-product depends on the water presence in cleavage mixture. Furthermore, the final deprotection of amide analogues of apelin-12 was accompanied by the formation of a by-product — 4-hydroxybenzylamide; its amount ranged from 20% to 8% in the reaction mixture (according to HPLC data) and also depended on the composition of the cleavage mixture. Effects of the synthesized peptides on recovery of the 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 with the control. Cardioprotective efficacy of the peptides increased in the following rank (I) < (II) = (III) < (IV) = (V).
Databáze: OpenAIRE
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