Literature DB >> 34506932

Synthesis and structural characterization of a monocarboxylic inhibitor for GRB2 SH2 domain.

Tao Xiao1, Luxin Sun1, Min Zhang1, Zilu Li2, Eric B Haura3, Ernst Schonbrunn4, Haitao Ji5.   

Abstract

A monocarboxylic inhibitor was designed and synthesized to disrupt the protein-protein interaction (PPI) between GRB2 and phosphotyrosine-containing proteins. Biochemical characterizations show compound 7 binds with the Src homology 2 (SH2) domain of GRB2 and is more potent than EGFR1068 phosphopeptide 14-mer. X-ray crystallographic studies demonstrate compound 7 occupies the GRB2 binding site for phosphotyrosine-containing sequences and reveal key structural features for GRB2-inhibitor binding. This compound with a -1 formal charge offers a new direction for structural optimization to generate cell-permeable inhibitors for this key protein target of the aberrant Ras-MAPK signaling cascade.
Copyright © 2021 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  GRB2; Inhibitors; Macrocyclic peptides; Protein-Protein Interaction; Ras-MAPK signaling; SH2 domains; X-ray crystallography

Mesh：

Substances：

Year:  2021        PMID： 34506932      PMCID： PMC8526398          DOI： 10.1016/j.bmcl.2021.128354

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  57 in total

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Authors:  Jean-Philippe Luzy; Huixiong Chen; Brunilde Gril; Wang-Qing Liu; Michel Vidal; Dominique Perdereau; Anne-Françoise Burnol; Christiane Garbay
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4.  Structure-based design, synthesis, and X-ray crystallography of a high-affinity antagonist of the Grb2-SH2 domain containing an asparagine mimetic.

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Journal:  J Med Chem       Date:  1999-07-01       Impact factor: 7.446

5.  N-terminal carboxyl and tetrazole-containing amides as adjuvants to Grb2 SH2 domain ligand binding.

Authors:  T R Burke; Z J Yao; Y Gao; J X Wu; X Zhu; J H Luo; R Guo; D Yang
Journal:  Bioorg Med Chem       Date:  2001-06       Impact factor: 3.641

6.  Thermodynamic and Structural Effects of Macrocyclization as a Constraining Method in Protein-Ligand Interactions.

Authors:  John E Delorbe; John H Clements; Benjamin B Whiddon; Stephen F Martin
Journal:  ACS Med Chem Lett       Date:  2010-11-11       Impact factor: 4.345

Review 7.  SRC homology-2 inhibitors: peptidomimetic and nonpeptide.

Authors:  Tomi K Sawyer; Regine S Bohacek; David C Dalgarno; Charles J Eyermann; Noriyuki Kawahata; Chester A Metcalf; William C Shakespeare; Raji Sundaramoorthi; Yihan Wang; Michael G Yang
Journal:  Mini Rev Med Chem       Date:  2002-10       Impact factor: 3.862

8.  Crystal structures of a high-affinity macrocyclic peptide mimetic in complex with the Grb2 SH2 domain.

Authors:  Jason Phan; Zhen-Dan Shi; Terrence R Burke; David S Waugh
Journal:  J Mol Biol       Date:  2005-10-14       Impact factor: 5.469

9.  A novel macrocyclic tetrapeptide mimetic that exhibits low-picomolar Grb2 SH2 domain-binding affinity.

Authors:  Zhen-Dan Shi; Kyeong Lee; Hongpeng Liu; Manchao Zhang; Lindsey R Roberts; Karen M Worthy; Matthew J Fivash; Robert J Fisher; Dajun Yang; Terrence R Burke
Journal:  Biochem Biophys Res Commun       Date:  2003-10-17       Impact factor: 3.575

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Authors:  Terrence R Burke
Journal:  Int J Pept Res Ther       Date:  2006-03-14       Impact factor: 1.931
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  1 in total

1.  The structural basis of BCR-ABL recruitment of GRB2 in chronic myelogenous leukemia.

Authors:  Yonglan Liu; Hyunbum Jang; Mingzhen Zhang; Chung-Jung Tsai; Ryan Maloney; Ruth Nussinov
Journal:  Biophys J       Date:  2022-05-31       Impact factor: 3.699
  1 in total

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