Structure-activity studies of highly potent cyclic [Cys4,Cys10]Melanotropin analogues.
Structure-activity studies of highly potent cyclic [Cys4,Cys10]Melanotropin analogues.
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高效环状 [Cys4,Cys10]促黑素类似物的结构-活性研究。
DOI：
10.1021/jm00356a002
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发表时间：
1983
影响因子：
7.3
通讯作者：
Hadley,ME
中科院分区：
文献类型：
--
作者：
Knittel,JJ;Sawyer,TK;Hruby,VJ;Hadley,ME
已经提出14，涉及促黑素细胞激素（-MSH）中的残基His-Phe-Arg-Trp的反转或其他链反转结构有助于该肽激素的生物活性构象。该建议得到以下观察结果的支持：[Cys 4，Cys 10]-α-MSH在青蛙皮肤生物测定中表现出超激动剂（> 10000 α-MSH）活性，并且在蜥蜴皮肤生物测定中效力高约30倍。本文进一步研究了[Cys_4，Cys_10]-α-MSH_4_10-NH_2和Ac-[Cys_4，Cys_10]-α-MSH_4_13-NH_2的生物活性。在蛙皮和蜥蜴皮生物测定中，发现环状4-10-七肽的活性低于-MSH，但比其线性同源物强得多（100倍）。Ac-a-MSH_4_10-NH_2在蛙体内的分布。用环状4-13-十肽，在青蛙皮肤上观察到超激动剂效力（等效于环状十三肽），并且在蜥蜴皮肤测定中类似物等效于MSH。这些结果支持了这样的建议，即在-MSH中的环状反转构象起着重要的作用。
It has been proposed14 that a ß turn or other chain-reversal structure involving the residues His-Phe-Arg-Trp in-melanocyte stimulating hormone (-MSH) contributes to the bioactive conformation of this peptide hormone. This proposal is supported by the observation that [Cys4, Cys10]--MSH exhibits superagonist (> 10000 a-MSH) activity in the frog skin bioassay and is about 30 times more potent in the lizard skin bioassay. Studies on the possible role of a reverse turn in the biological activities of [Cys4, Cys10]--MSH have been extended with the synthesis ofAc-[Cys4, Cys10]-a-MSH4-10-NH2 and Ac-[Cys4, Cys10]-a-MSH4_13-NH2. The cyclic 4-10-heptapeptide was found to be less active than-MSH inboth the frogand lizard skin bioassays, but much more potent (100 times) than its linear congener. Ac-a-MSH4_10-NH2 in thefrog. With the cyclic 4-13-decapeptide, superagonist potency (equipotent to the cyclic tridecapeptide) was observed on the frog skin, and the analogue was equipotent to-MSH in the lizard skin assay. These results support the suggestion that a cyclic reverse-turn conformation in-MSH plays a significant