Kuczer M, Rosiński G, Issberner J, Osborne R, Konopińska D
Faculty of Chemistry, University of Wrocław, Poland.
Pol J Pharmacol. 1998 Mar-Apr;50(2):143-50.
We have extended our work on structure/activity relationship of neuropeptide proctolin (H-Arg-Tyr-Leu-Pro-Thr-OH) by evaluating the effects of the following proctolin analogues: H-X1-Tyr-Leu-Pro-Thr-OH, where X1 = D-Arg (1), N-Me-Arg (2), Can (3), D-Tyr2, D-Leu3, D-Thr5]-proctolin (12). In analogues 1-9, the N-terminal Arg-residue was replaced by basic amino acid derivatives with peptides containing amino acid residues with an isosteric system on the back side chain relative to Arg (compounds 3, 5 and 6) or homo-Arg (compound 7). Analogues 1-12 were evaluated for myotropic action on in vitro heart preparation of Tenebrio molitor, whereas peptides 2, 5 and 7-12 were tested for contractile action on isolated foregut of Schistocerca gregaria. Peptides 2 and 3 retained full cardiotropic activity in Tenebrio molitor while peptides 5 and 7 preserved 40% and 15%, respectively, locust-gut contracting activity of proctolin. Peptides 11 and 12 showed antagonistic activity in Schistocerca gregaria foregut.
我们通过评估以下促肠动肽类似物的作用，扩展了对神经肽促肠动肽（H-精氨酸-酪氨酸-亮氨酸-脯氨酸-苏氨酸-OH）结构/活性关系的研究：H-X1-酪氨酸-亮氨酸-脯氨酸-苏氨酸-OH，其中X1 = D-精氨酸（1）、N-甲基-精氨酸（2）、瓜氨酸（3）、[D-酪氨酸2、D-亮氨酸3、D-苏氨酸5]-促肠动肽（12）。在类似物1-9中，N端的精氨酸残基被碱性氨基酸衍生物取代，这些肽含有相对于精氨酸在侧链背面具有等排体系的氨基酸残基（化合物3、5和6）或高精氨酸（化合物7）。对类似物1-12在黄粉虫体外心脏制剂上的肌动作用进行了评估，而对肽2、5和7-12在沙漠蝗分离前肠上的收缩作用进行了测试。肽2和3在黄粉虫中保留了完全的强心活性，而肽5和7分别保留了促肠动肽40%和15%的蝗虫肠道收缩活性。肽11和12在沙漠蝗前肠中表现出拮抗活性。
