Solution structure of a cyclic RGD peptide that inhibits platelet aggregation.
Solution structure of a cyclic RGD peptide that inhibits platelet aggregation.
复制标题
DOI：
10.1080/07391102.1996.10508923
复制
发表时间：
1996
影响因子：
4.4
通讯作者：
S. Jois;U. S. Tambunan;S. Chakrabarti;T. Siahaan
中科院分区：
文献类型：
--
作者：
S. Jois;U. S. Tambunan;S. Chakrabarti;T. Siahaan
含有精氨酸-甘氨酸-天冬氨酸（RGD）序列的肽可以抑制血小板聚集。将该序列掺入环肽中会导致与特定整合素的特异性结合。对环状 RGD 肽的研究表明，RGD 序列周围的残基对该肽与糖蛋白 IIb/IIIa (GPIIb/IIIa) 结合的选择性具有重要影响。在本文中，我们通过核磁共振和分子动力学模拟阐明了环(2,10)Ac-Gly1-Pen2-Gly3-His4-Arg5-Gly6-Asp7 -Leu8-Arg9-Cys10-Ala11-NH2 (1) 的构象。该肽以与 cyclo(2,10)Gly1-Pen2-Gly3-His4-Arg5-Gly6-Asp7-Le u8-Arg9-Cys10-Ala11-OH (6) 报道类似的方式抑制血小板聚集（Cheng, S. 等人 J. Med. Chem. 1994, 37, 1-8），显示对GPIIb/IIIa 受体。环肽1在溶液中表现出主要构象异构体和次要构象异构体。在主要构象异构体中，His4-Arg5-Gly6-Asp7 片段包含具有扭曲的 II 型 β 转角的 4-->1 氢键，次要构象异构体具有转角延伸转角。该肽的主要构象与其他环状 RGD 肽的主要构象之间的比较表明与 RGD 序列相邻的疏水残基的重要性。
Peptides containing the Arg-Gly-Asp (RGD) sequence can inhibit platelet aggregation. Incorporation of this sequence into a cyclic peptide results in specific binding to a particular integrin. Studies of cyclic RGD peptides show that residues surrounding the RGD sequence have important effects on the selectivity of the peptide to bind with glycoprotein IIb/IIIa (GPIIb/IIIa). In this paper, we elucidate the conformation of cyclo(2,10)Ac-Gly1-Pen2-Gly3-His4-Arg5-Gly6-Asp7 -Leu8-Arg9-Cys10-Ala11-NH2 (1) by NMR and molecular dynamics simulations. This peptide inhibits platelet aggregation in a manner similar to that reported for cyclo(2,10)Gly1-Pen2-Gly3-His4-Arg5-Gly6-Asp7-Le u8-Arg9-Cys10-Ala11-OH (6) (Cheng, S. et al. J. Med. Chem. 1994, 37, 1-8), which is shown to be selective for the GPIIb/IIIa receptor. The cyclic peptide 1 exhibited a major and a minor conformer in solution. In the major conformer, the His4-Arg5-Gly6-Asp7 segment encompasses a 4-->1 hydrogen bond with a distorted type II beta-turn, and the minor conformer has turn-extended-turn. A comparison between the major conformation of this peptide and those of other cyclic RGD peptides suggests the importance of a hydrophobic residue adjacent to the RGD sequence.