A synthetic human Agouti‐related protein‐(83–132)‐NH2 fragment is a potent inhibitor of melanocortin receptor function
A synthetic human Agouti‐related protein‐(83–132)‐NH2 fragment is a potent inhibitor of melanocortin receptor function
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DOI：
10.1016/s0014-5793(98)00487-6
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发表时间：
1998-05
期刊：
影响因子：
3.5
通讯作者：
J. Quillan;W. Sadee;Edward T. Wei;Charles C. Jimenez;Li Ji;J. Chang
中科院分区：
文献类型：
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作者：
J. Quillan;W. Sadee;Edward T. Wei;Charles C. Jimenez;Li Ji;J. Chang
Agouti蛋白质- Agouti和Agouti相关蛋白质-的化学合成由于其大尺寸和位于羧基末端区域的多个半胱氨酸残基而变得复杂。合成了三种人Agouti相关蛋白（AGRP）片段，其中两种对应于氨基酸82和83之间的建议内切蛋白酶切割位点，并使用非洲爪蟾皮肤黑色素细胞测试了抗促黑素活性。氨基末端片段AGRP（25-51）和（54-82）没有显著的拮抗活性，而酰胺化羧基末端AGRP片段（83-132）-NH 2具有有效活性，抑制平衡解离常数（Ki）为0.7 nM。合成功能活性AGRP的能力应有助于阐明其在中枢神经系统中的作用及其与G蛋白偶联受体的黑皮质素家族相互作用的不寻常性质。
Chemical synthesis of Agouti proteins – Agouti and Agouti-related proteins – is complicated by their large size and by multiple cysteine residues located in the carboxyl terminal regions. Three human Agouti-related protein (AGRP) fragments, two of which correspond to a proposed endoprotease cleavage site between amino acids 82 and 83, were synthesized and tested for anti-melanotropic activity using Xenopus laevis dermal melanophores. Amino-terminal fragments AGRP(25–51) and (54–82) were devoid of significant antagonist activity, whereas the amidated carboxyl-terminal AGRP fragment (83–132)-NH2was potently active with an inhibitory equilibrium dissociation constant (Ki) of 0.7 nM. The ability to synthesize functionally active AGRP should help unravel its role in the central nervous system and its unusual properties with respect to interaction with the melanocortin family of G-protein coupled receptors.