Synthesis and biological actions of highly potent and prolonged acting biotin-labeled melanotropins.
Synthesis and biological actions of highly potent and prolonged acting biotin-labeled melanotropins.
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DOI：
10.1021/jm00377a005
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发表时间：
1984-11
影响因子：
7.3
通讯作者：
D. N. Chaturvedi;J. Knittel;V. Hruby;A. M. Castrucci;M. Hadley
中科院分区：
文献类型：
--
作者：
D. N. Chaturvedi;J. Knittel;V. Hruby;A. M. Castrucci;M. Hadley
制备了 α-促黑素激素超强类似物 [Nle4,D-Phe7]-α-MSH 的生物胞素衍生物。采用固相技术合成了[N α-Bct-Ser1,Nle4,D-Phe7]-α-MSH和[12-Bct-N α-十二酰基-Ser1,Nle4,D-Phe 7]-α-MSH，并通过其琥珀酰亚胺酯实现了生物素与12-氨基十二烷酸的偶联。根据多项黑素细胞生物测定的结果，这些促黑素细胞具有与 [Nle4,D-Phe 7]-α-MSH 几乎相同的作用。两种生物胞素衍生物都是高效激动剂，并在青蛙和蜥蜴皮肤生物测定中显示出持久的生物活性。两种生物素化肽在刺激 Cloudman S91 小鼠黑色素瘤酪氨酸酶活性方面至少与 α-MSH 等效。该类似物对α-胰凝乳蛋白酶的灭活具有抵抗力。
Biocytin derivatives of a superpotent analogue of alpha-melanotropin, [Nle4,D-Phe7]-alpha-MSH, were prepared. [N alpha-Bct-Ser1, Nle4,D-Phe7]-alpha-MSH and [12-Bct-N alpha-dodecanoyl-Ser1,Nle4,D-Phe 7]- alpha-MSH were synthesized by solid-phase techniques, and the coupling of biotin and 12-aminododecanoic acid was achieved through their succinimido esters. These melanotropins possessed almost identical actions to [Nle4,D-Phe 7]- alpha-MSH as determined by several melanocyte bioassays. Both biocytin derivatives were highly potent agonists and exhibited prolonged biological activity as determined in the frog and lizard skin bioassays. Both biotinylated peptides were at least equipotent to alpha-MSH in stimulating Cloudman S91 mouse melanoma tyrosinase activity. The analogues were resistant to inactivation by alpha-chymotrypsin.