Discovery of Trp-Nle-Tyr-Met as a novel agonist for human formyl peptide receptor-like 1
文献类型：期刊论文
| 作者 | Wan, Hui-Xin; Zhou, Caihong; Zhang, Yueyun; Sun, Meiling; Wang, Xin ; Yu, Hong; Yang, Xiaoke; Ye, Richard D.; Shen, Jing Kang; Wang, Ming-Wei
|
| 刊名 | BIOCHEMICAL PHARMACOLOGY
 |
| 出版日期 | 2007-07-15 |
| 卷号 | 74期号:2页码:317-326 |
| 关键词 | formyl peptide receptor-like 1 chemotactic peptides Trp-Lys-Tyr-Met-Val-[D]Met structure-activity relationship peptidomimetic |
| ISSN号 | 0006-2952 |
| DOI | 10.1016/j.bcp.2007.04.016 |
| 文献子类 | Article |
| 英文摘要 | Forrnyl peptide receptor-like 1 (FPRL1) is a structural homologue of FPR, which binds chemotactic peptides as small as three amino acids (e.g., fMet-Leu-Phe, fMLF) and activates potent bactericidal functions in neutrophils. In comparison, FPRL1 ligands include peptides of 6-104 amino acids, such as Trp-Lys-Tyr-Met-Val-[D]Met (WKYMVm) and other synthetic peptides. To determine the core peptide sequence required for FPRL1 activation, we prepared various analogues based on WKYMVm and evaluated their bioactivities in an FPRL1 -trans fected cell line. Although substitution of D-Met(6) resulted in loss of activity, removal of Val(5) together with D-Met(6) produced a peptide that retained most of the bioactivities of the parent peptide. The resulting peptide, WKYM, represents a core structure for an FPRL1 ligand. Further substitution of Lys' with Nle slightly improved the potency of the tetrapeptide, which selectively activates FPRL1 over FPR. Based on these structure-activity relationship studies, we propose a model in which the modified tetrapeptide Trp -Nle-Tyr- Met (WNleYM) binds to FPRL1 through aromatic interactions involving the side chains of Trp(1) and Tyr(3), hydrophobic interaction of Nle(2), and the thio-based hydrogen bonding of Met(4), with the respective residues in FPRL1 which have not been identified. The identification of the core sequence of a potent peptide agonist provides a structural basis for future design of peptidomimetics as potential therapeutic agents for FPRL1-related disorders. (C) 2007 Elsevier Inc. All rights reserved. |
| WOS关键词 | PROTEIN-COUPLED RECEPTORS ; VAL-D-MET ; CHEMOATTRACTANT RECEPTOR ; DIFFERENTIAL ACTIVATION ; CHEMOTACTIC AGONIST ; LIGAND-BINDING ; IDENTIFICATION ; CDNA ; 7-TRANSMEMBRANE ; DOMAINS |
| 资助项目 | NIAID NIH HHS[AI033503] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000248160700014 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273200]  |
| 专题 | 药物化学研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 国家新药筛选中心 |
| 通讯作者 | Shen, Jing Kang |
| 作者单位 | 1.Univ Illinois, Dept Pharmacol, Chicago, IL USA 2.Natl Ctr Drug Screening, Shanghai, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wan, Hui-Xin,Zhou, Caihong,Zhang, Yueyun,et al. Discovery of Trp-Nle-Tyr-Met as a novel agonist for human formyl peptide receptor-like 1[J]. BIOCHEMICAL PHARMACOLOGY,2007,74(2):317-326. |
| APA | Wan, Hui-Xin.,Zhou, Caihong.,Zhang, Yueyun.,Sun, Meiling.,Wang, Xin.,...&Wang, Ming-Wei.(2007).Discovery of Trp-Nle-Tyr-Met as a novel agonist for human formyl peptide receptor-like 1.BIOCHEMICAL PHARMACOLOGY,74(2),317-326. |
| MLA | Wan, Hui-Xin,et al."Discovery of Trp-Nle-Tyr-Met as a novel agonist for human formyl peptide receptor-like 1".BIOCHEMICAL PHARMACOLOGY 74.2(2007):317-326. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。