Baker B I, Kinsman R G, Moss C A, White P D, Paul P K, Brown D W, Campbell M M, Osguthorpe D J
School of Biological Sciences, Bath University, U.K.
Peptides. 1990 Nov-Dec;11(6):1103-8. doi: 10.1016/0196-9781(90)90137-t.
A number of cyclic and linear fragments and analogues of MCH were synthesized and their biological potencies tested using the isolated carp scale melanophore assay. In this system the cyclic portion MCH(5-14) exhibited only 0.1% bioactivity, which was markedly enhanced by the addition of the exocyclic sequences MCH(15-17) and MCH(1-4). The exocyclic sequence itself, MCH(1-4,15-17), had minimal activity, however. Substitution of Tyr11 with phenylalanine reduced the potency of the ring structure MCH(5-14) by about 4-fold. Substitution of Gly8 with D-alanine reduced the potency of MCH(5-14) 16-fold, while both substitutions together caused a still more marked reduction (200-fold) in bioactivity. Linearized fragments of MCH, extending from MCH(15-17) to [Cys(Acm)5,14]MCH(1-17), showed a progressive increase in potency. The linearized forms of MCH, MCH(5-17) and MCH(5-14), were approximately 100-fold or less potent than their cyclic forms. The significant increases in bioactivity produced by the addition of the C- and N-terminal exocyclic sequence even to these linearized forms further emphasizes the importance of these regions for interaction at the receptor site.
合成了多种促黑素细胞激素（MCH）的环状和线性片段及其类似物，并使用分离的鲤鱼鳞片黑素细胞试验检测了它们的生物活性。在该系统中，环状部分MCH(5 - 14)仅表现出0.1%的生物活性，通过添加环外序列MCH(15 - 17)和MCH(1 - 4)，其生物活性显著增强。然而，环外序列本身，即MCH(1 - 4,15 - 17)，活性极小。用苯丙氨酸取代Tyr11使环结构MCH(5 - 14)的活性降低约4倍。用D - 丙氨酸取代Gly8使MCH(5 - 14)的活性降低16倍，而这两种取代共同作用导致生物活性更显著降低（200倍）。从MCH(15 - 17)延伸至[Cys(Acm)5,14]MCH(1 - 17)的MCH线性片段活性逐渐增加。MCH的线性形式MCH(5 - 17)和MCH(5 - 14)的活性比其环状形式低约100倍或更低。即使向这些线性形式添加C端和N端环外序列也能显著提高生物活性，这进一步强调了这些区域在受体位点相互作用中的重要性。
