Effects of conformational constraint in 2- and 8-cycloleucine analogues of oxytocin and [1-penicillamine] oxytocin examined by circular dichroism and bioassay.
Effects of conformational constraint in 2- and 8-cycloleucine analogues of oxytocin and [1-penicillamine] oxytocin examined by circular dichroism and bioassay.
复制标题
通过圆二色性和生物测定检查催产素和[1-青霉胺]催产素的2-和8-环亮氨酸类似物的构象限制的影响。
DOI：
10.1007/bf01024978
复制
发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Hruby,VJ
中科院分区：
文献类型：
--
作者：
Fric,I;Hlavacek,J;Rockway,TW;Chan,WY;Hruby,VJ
用圆二色谱法研究了缩宫素和[1-青霉胺]缩宫素在2位或8位含有环亮氨酸（Cle）残基的类似物在不同溶剂中的性质，并对其生物活性进行了研究。2位的环亮氨酸残基基本上减少了激素20元环部分（包括二硫键基团）的自由构象空间，并稳定了与催产素的可能构象之一接近并涉及β-转角的构象。在位置8，Cle残基影响Tyr 2侧链的构象，显然迫使其远离20元二硫环上方的空间。然而，似乎Cle残基对激素的总体骨架构象没有任何显著影响。进一步证实了1位青霉胺残基对二硫基和Tyr 2侧链构象的空间效应。本文报道了[1-青霉胺，8-环亮氨酸]催产素的合成及其生物活性。该类似物在体外对催产素的子宫收缩活性有很强的抑制作用。它还抑制了对加压素的加压反应。
The analogues of oxytocin and [1-penicillamine]oxytocin, containing a cycloleucine (Cle) residue in position 2 or 8, were investigated by means of circular dichroism measurements in different solvents, and the results examined in terms of their biological activities. A cycloleucine residue in position 2 substantially reduces the free conformational space of the hormone 20-membered ring moiety (including the disulfide group), and stabilizes a conformation which is close to one of the possible conformations of oxytocin and involves a β-turn. In position 8, the Cle residue affects the conformation of the Tyr2side chain, apparently forcing it away from the space above the 20-membered disulfide ring. However, it does not appear that the Cle residue has any significant effect on the overall backbone conformation of the hormone. The steric effect of the penicillamine residue in position 1 on the conformation of the disulfide group and Tyr2side chain from previous investigations is further confirmed. The synthesis and biological potency of [1-penicillamine, 8-cycloleucine]oxytocin is described. This analogue exhibits a strong inhibitory effect on the uterotonic activity of oxytocinin vitro. It also inhibited the vasopressor response to vasopressin.