Odell B, Hammond S J, Osborne R, Goosey M W
Shell Research Ltd, Sittingbourne Research Centre, Kent, U.K.
J Comput Aided Mol Des. 1996 Apr;10(2):89-99. doi: 10.1007/BF00402817.
Proctolin (Arg-Tyr-Leu-Pro-Thr) was the first insect neuropeptide to be chemically characterised. It plays an essential role in insect neurophysiology and is involved in muscular contraction and neuromodulation. Elements of secondary structure in solution have been studied by comparing data obtained from NMR and molecular dynamics simulations. Different secondary structural requirements are associated with agonist and antagonist activities. A favoured conformation of proctolin has an inverse gamma-turn, comprising an intramolecular hydrogen bond near the C-terminal end between Thr NH and Leu CO. Antagonists have a more compact structure resembling a 'paperclip' loop, containing an intramolecular hydrogen bond between Tyr NH and Pro CO, possibly stabilised by a salt bridge between the N- and C-terminal groups. A cyclic analogue retains antagonist activity and resembles a beta-bulge loop, also comprising intramolecular hydrogen bonds between Tyr NH and Pro CO and Thr CO. These models may offer feasible starting points for designing novel compounds with proctolinergic activity.
促肠动素（Arg-Tyr-Leu-Pro-Thr）是首个经化学表征的昆虫神经肽。它在昆虫神经生理学中发挥着重要作用，参与肌肉收缩和神经调节。通过比较从核磁共振（NMR）和分子动力学模拟获得的数据，对溶液中的二级结构元素进行了研究。不同的二级结构要求与激动剂和拮抗剂活性相关。促肠动素的一种有利构象具有反向γ-转角，在苏氨酸（Thr）的NH和亮氨酸（Leu）的CO之间的C末端附近包含一个分子内氢键。拮抗剂具有更紧凑的结构，类似于一个“回形针”环，在酪氨酸（Tyr）的NH和脯氨酸（Pro）的CO之间包含一个分子内氢键，可能由N端和C端基团之间的盐桥稳定。一种环状类似物保留了拮抗剂活性，类似于一个β-凸起环，也在酪氨酸（Tyr）的NH和脯氨酸（Pro）的CO以及苏氨酸（Thr）的CO之间包含分子内氢键。这些模型可能为设计具有促肠动素活性的新型化合物提供可行的起点。
