Discovery of 3-aminobenzyloxycarbonyl as an N-terminal group conferring high affinity to the minimal phosphopeptide sequence recognized by the Grb2-SH2 domain
Discovery of 3-aminobenzyloxycarbonyl as an N-terminal group conferring high affinity to the minimal phosphopeptide sequence recognized by the Grb2-SH2 domain
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DOI：
10.1021/jm9702185
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发表时间：
1997-10-24
影响因子：
7.3
通讯作者：
Caravatti, G
中科院分区：
文献类型：
--
作者：
Furet, P;Gay, B;Caravatti, G
邻氨基苯甲酸作为N-末端基团产生的磷酸肽序列Glu-pTyr-Ile-Asn的Grb 2-SH 2结构域的结合亲和力的显着增加的观察是合理的分子建模。该模型，其中调用的N-末端基团和SH 2结构域残基Arg α A2之间的堆叠相互作用，随后用于设计3-氨基苄氧羰基N-末端基团。后者赋予Grb 2-SH 2结构域识别的最小序列pTyr-Ile-Asn高亲和力（在ELISA测定中IC 50 = 65 nM）。
The observation that anthranilic acid as N-terminal group produces a dramatic increase of the binding affinity of the phosphopeptide sequence Glu-pTyr-Ile-Asn for the Grb2-SH2 domain was rationalized by molecular modeling. The model, which invokes a stacking interaction between the N-terminal group and the SH2 domain residue Arg alpha A2, was subsequently used to design the 3-aminobenzyloxycarbonyl N-terminal group. The latter confers high affinity (IC50 = 65 nM in an ELISA assay) to the minimal sequence pTyr-Ile-Asn recognized by the Grb2-SH2 domain.