Mapping the X+1 binding site of the Grb2-SH2 domain with α,α-disubstituted cyclic α-amino acids
Mapping the X+1 binding site of the Grb2-SH2 domain with α,α-disubstituted cyclic α-amino acids
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DOI：
10.1016/s0960-894x(99)00501-6
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发表时间：
1999-10-18
影响因子：
2.7
通讯作者：
Furet, P
中科院分区：
文献类型：
--
作者：
García-Echeverría, C;Gay, B;Furet, P
合成了一系列在 Ac-Tyr(PO3H2)-X+1-Asn-NH2 的 X+1 位含有 α,α-二取代的环状 α-氨基酸（Ac(n)c, 3 ≤ n ≤ 7; n 指环中的碳数）的磷酸肽，并作为其拮抗剂的抑制活性。 Grb2-SH2 结构域已在竞争性结合测定中确定。获得的 SAR 数据已通过使用由配体结合的 Grb2-SH2 结构域的 X 射线结构构建的模型进行了解释。使用α,α-二取代的环状α-氨基酸来绘制蛋白质的结合袋图谱扩展了经典的丙氨酸扫描概念，并利用了这些氨基酸的已知构象偏好。 (C) 1999 Elsevier Science Ltd. 保留所有权利。
A series of phosphopeptides containing alpha,alpha-disubstituted cyclic alpha-amino acids (Ac(n)c, 3 less than or equal to n less than or equal to 7; n refers to the number of carbons in the ring) at the X+1 position of Ac-Tyr(PO3H2)-X+1-Asn-NH2 has been synthesised and their inhibitory activity as antagonists of the Grb2-SH2 domain has been determined in competitive binding assays. The SAR data obtained have been interpreted by using models constructed from the X-ray structure of the ligand-bound Grb2-SH2 domain. The used of alpha,alpha-disubstituted cyclic alpha-amino acids to map the binding pockets of proteins expands the classical alanine scan concept and takes advantage of the known conformational preferences of these amino acids. (C) 1999 Elsevier Science Ltd. All rights reserved.