具有纳摩尔级结合亲和力的环状酰胺混合 α-MSH/Agouti 相关蛋白 (AGRP) 类似物，可与人类黑皮质素受体结合。
Cyclic lactam hybrid α-MSH/Agouti-related protein (AGRP) analogues with nanomolar range binding affinities at the human melanocortin receptors.
机构信息
Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA.
出版信息
Bioorg Med Chem Lett. 2011 May 15;21(10):3099-102. doi: 10.1016/j.bmcl.2011.03.019. Epub 2011 Mar 13.
Abstract
A novel hybrid melanocortin pharmacophore was designed based on the topographical similarities between the pharmacophores of Agouti related protein (AGRP) an endogenous melanocortin antagonist, and α-melanocyte-stimulating hormone (α-MSH), an endogenous melanocortin agonist. When employed in two different 23-membered macrocyclic lactam peptide templates, the designed hybrid AGRP/MSH pharmacophore yielded non-competitive ligands with nanomolar range binding affinities. The topography-based pharmacophore hybridization strategy will prove useful in development of unique non-competitive melanocortin receptor modulators.
摘要
基于 Agouti 相关蛋白（AGRP）和α-促黑素细胞激素（α-MSH）两种内源性黑色素促激素激动剂和拮抗剂的药效团拓扑相似性，设计了一种新型混合黑色素促激素药效团。将设计的混合 AGRP/MSH 药效团应用于两种不同的 23 元大环内酰胺肽模板中，得到了具有纳摩尔范围结合亲和力的非竞争性配体。基于拓扑结构的药效团杂交策略将有助于开发独特的非竞争性黑色素促激素受体调节剂。
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