基于结构的Grb2-SH2结构域拟肽配体设计。

Structure-based design of peptidomimetic ligands of the Grb2-SH2 domain.

作者信息

Schoepfer J, Gay B, Caravatti G, Garcia-Echeverria C, Fretz H, Rahuel J, Furet P

机构信息

Novartis Pharma Inc., Oncology Research Department, Basle, Switzerland.

出版信息

Bioorg Med Chem Lett. 1998 Oct 20;8(20):2865-70. doi: 10.1016/s0960-894x(98)00513-7.

DOI:10.1016/s0960-894x(98)00513-7

PMID:9873638

Abstract

We have designed and synthesized a (3-aminomethyl-phenyl)-urea scaffold to mimic the X+1-Asn part of the minimal phosphopeptide sequence, Ac-pTyr-X+1-Asn-NH2, recognized by the Grb2-SH2 domain. The resulting compounds show the same degree of affinity as their peptide counterparts for the Grb2-SH2 domain. This is the first example reported to date of ligands of the Grb2-SH2 domain with substantially reduced peptidic character.

摘要

我们设计并合成了一种（3-氨甲基-苯基）-脲支架，以模拟被Grb2-SH2结构域识别的最小磷酸肽序列Ac-pTyr-X +1-Asn-NH2中的X +1-Asn部分。所得化合物对Grb2-SH2结构域显示出与相应肽相同程度的亲和力。这是迄今为止报道的具有显著降低肽性的Grb2-SH2结构域配体的首个实例。