Kuczer M, Rosiński G, Lisowski M, Picur B, Konopiñska D
Faculty of Chemistry, University of Wrocław, Poland.
Int J Pept Protein Res. 1996 Sep;48(3):286-91. doi: 10.1111/j.1399-3011.1996.tb00843.x.
The object of our studies was the synthesis and conformational and biological evaluation of the series of 14 analogues of the insect neuropeptide, proctolin. The analogues were obtained by replacement of the native L-amino acids by their D-isomers in one, two, and all positions. Biological effects of the peptides were examined by cardioexcitatory test on the heart of yellow mealworm, Tenebrio molitor, in vitro. In biotest performed on insects, D-Arg-D-Tyr-D-Leu-D-Pro-D-Thr, [D-Arg(N-G-nitro)1,D-Leu3]-, [D-Arg1,D-Leu3]-, [D-Tyr2,D-Thr5]- and [D-Arg1,D-Pro4]-proctolin exert high agonistic activity of proctolin on the heart of insects at 10(-11) - 10(-10) M concentrations. The proctolin analogue containing only D-amino acid residues in the peptide chain unexpectedly shows a much higher cardioexcitatory effect than the native peptide. Moreover, preliminary CD and NMR conformational studies show that proctolin analogues investigated here seem to prefer rather ordered structures, although their conformations differ in some cases.
我们研究的目标是合成昆虫神经肽原肌球蛋白的14种类似物，并对其进行构象和生物学评估。这些类似物是通过在一个、两个以及所有位置将天然L-氨基酸替换为其D-异构体而获得的。通过对黄粉虫（Tenebrio molitor）心脏进行体外心脏兴奋试验来检测这些肽的生物学效应。在对昆虫进行的生物测试中，D-Arg-D-Tyr-D-Leu-D-Pro-D-Thr、[D-Arg(N-G-硝基)1,D-Leu3]-、[D-Arg1,D-Leu3]-、[D-Tyr2,D-Thr5]-和[D-Arg1,D-Pro4]-原肌球蛋白在10(-11)-10(-10)M浓度下对昆虫心脏表现出高原肌球蛋白激动活性。肽链中仅含D-氨基酸残基的原肌球蛋白类似物意外地显示出比天然肽更高的心脏兴奋作用。此外，初步的圆二色光谱（CD）和核磁共振（NMR）构象研究表明，此处研究的原肌球蛋白类似物似乎更倾向于相当有序的结构，尽管它们的构象在某些情况下有所不同。
