固相法合成心肌兴奋肽及其类似物

用Boc-和Tos-基团分别保护氨基和侧链胍基,以1%交联度聚苯乙烯二苯甲氨基树脂为载体,用DCC固相法合成肽,HF断裂肽树脂键和去除侧链保护基团,粗产物经高效液相层析纯化,合成了心肌兴奋肽Phe-Met-Arg-Phe-NH₂及其类似物Phe-Pro-Arg-Phe-NH₂,并观察了此二种肽对大鼠血压和心率的影响。

SOLID PHASE PEPTIDE SYNTHESIS OF CARDIOEXCITATORY PEPTIDE AND ITS ANALOG

Cordioexeitatory peptide (Phe-Met-Arg-Phe-NH₂, FMRF-NH₂) and its analog (Phe-Pro-Arg-Phe-NH₂, FPRF-NH2) were synthesized by a solid phase procedure on a benzhydrylamine resin. Boo-amino acids and Boc-Arg(Tos) were used. The course of the synthesis was monitored by quantitative ninhydrin analysis. Following cleavage by the 90% HF method the peptides were purified by reverse phase HPLC. The overall yields of homogeneous isolated peptides from the first amino acid were 36% and 37%, respectively. It was found that the cleavage of Tos from Arg is related to temperature. The efficacy of FMRF-NH₂ and FPRF-NH₂ as antagonists to the opioid peptide D-Ala², Leu⁵ enkephalin was tested, using changes in mean arterial blood pressure and heart rate as indices. Results indicate that the former is more potent than the latter.