Incorporation of a bioactive reverse-turn heterocycle into a peptide template using solid-phase synthesis to probe melanocortin receptor selectivity and ligand conformations by 2D 1H NMR.
Incorporation of a bioactive reverse-turn heterocycle into a peptide template using solid-phase synthesis to probe melanocortin receptor selectivity and ligand conformations by 2D 1H NMR.
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使用固相合成将生物活性回转杂环掺入肽模板中，通过 2D 1H NMR 探测黑皮质素受体选择性和配体构象。
DOI：
10.1021/jm101425m
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发表时间：
2011
影响因子：
7.3
通讯作者：
Haskell-Luevano,Carrie
中科院分区：
文献类型：
--
作者：
Singh,Anamika;Wilczynski,Andrzej;Holder,JerryR;Witek,RachelM;Dirain,MarvinL;Xiang,Zhimin;Edison,ArthurS;Haskell-Luevano,Carrie
By use of a solid-phase synthetic approach, a bioactive reverse turn heterocycle was incorporated into a cyclic peptide template to probe melanocortin receptor potency and ligand structural conformations. The five melanocortin receptor isoforms (MC1R−MC5R) are G-protein-coupled receptors (GPCRs) that are regulated by endogenous agonists and antagonists. This pathway is involved in pigmentation, weight, and energy homeostasis. Herein, we report novel analogues of the chimeric AGRP-melanocortin peptide template integrated with a small molecule moiety to probe the structural and functional consequences of the core His-Phe-Arg-Trp peptide domain using a reverse-turn heterocycle. A series of six compounds are reported that result in inactive to full agonists with nanomolar potency. Biophysical structural analysis [2D1H NMR and computer-assisted molecular modeling (CAMM)] were performed on selected analogues, resulting in the identification that these peptide-small molecule hybrids possessed increased flexibility and fewer discrete conformational families compared to the reference peptide and result in a novel template for further structure−function studies.
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影响因子：
2.9
作者：
Z. Xiang;I. Pogozheva;Nicholas B. Sorenson;A. Wilczynski;J. R. Holder;S. Litherland;W. Millard;H. Mosberg;C. Haskell-Luevano
通讯作者：
Z. Xiang;I. Pogozheva;Nicholas B. Sorenson;A. Wilczynski;J. R. Holder;S. Litherland;W. Millard;H. Mosberg;C. Haskell-Luevano
影响因子：
2.9
作者：
CHEN, WB;SHIELDS, TS;CONE, RD
通讯作者：
CONE, RD
影响因子：
56.9
作者：
MOUNTJOY, KG;ROBBINS, LS;CONE, RD
通讯作者：
CONE, RD
影响因子：
15
作者：
Doedens, Lucas;Opperer, Florian;Cai, Minying;Beck, Johannes G.;Dedek, Matt;Palmer, Erin;Hruby, Victor J.;Kessler, Horst
通讯作者：
Kessler, Horst
DOI：
10.1006/bbrc.1994.1580
发表时间：
1994-05-16
影响因子：
3.1
作者：
GANTZ, I;SHIMOTO, Y;YAMADA, T
通讯作者：
YAMADA, T