Multivalent effects of RGD peptides obtained by nanoparticle display
Multivalent effects of RGD peptides obtained by nanoparticle display
复制标题
DOI：
10.1021/jm060515m
复制
发表时间：
2006-10-05
影响因子：
7.3
通讯作者：
Josephson, Lee
中科院分区：
文献类型：
--
作者：
Montet, Xavier;Funovics, Martin;Josephson, Lee
RGD肽与整联蛋白的结合提供了一个极好的系统来研究当展示在纳米颗粒载体表面上的肽与展示在细胞膜上的整联蛋白结合时产生的多价介导的亲和力变化。RGD纳米颗粒对内皮粘附的IC 50为1.0 nM纳米颗粒或20 nM肽（20肽/纳米颗粒），并与强多价效应相关，定义为38的多价增强因子（MVE）（MVE = IC 50（肽）/IC 50（由纳米颗粒显示时的肽））。将RGD肽附着到纳米颗粒上导致肽的血液半衰期从13分钟延长到180分钟。基于亲和力的多价增强和血液半衰期的延长，多价RGD纳米颗粒大小的材料应该是体内内皮细胞上的alpha（V）beta（3）功能的有效抑制剂。
The binding of RGD peptides to integrins offers an excellent system to study the multivalent mediated changes in affinity that arise when peptides, displayed on the surface of a nanoparticle carrier, bind to integrins displayed on the cell membrane. The IC50 of an RGD nanoparticle for endothelial adhesion was 1.0 nM nanoparticle or 20 nM peptide (20 peptide/nanoparticle) and was associated with strong multivalent effects, defined as a multivalent enhancement factor (MVE) of 38 (MVE = IC50 (peptide)/IC50 (peptide when displayed by nanoparticle)). The attachment of RGD peptides to nanoparticles resulted in an extension of the peptide blood half-life from 13 to 180 min. Based on the multivalent enhancement of affinity and extension of blood half-life, multivalent RGD nanoparticle-sized materials should be potent inhibitors of the alpha(V) beta(3) function on endothelial cells in vivo.