Synthesis of a C-terminally biotinylated macrocyclic peptide mimetic exhibiting high Grb2 SH2 domain-binding affinity

Zhen Dan Shi; Hongpeng Liu; Manchao Zhang; Karen M. Worthy; Lakshman Bindu; Dajun Yang; Robert J. Fisher; Terrence R. Burke

doi:10.1016/j.bmc.2005.04.028

Synthesis of a C-terminally biotinylated macrocyclic peptide mimetic exhibiting high Grb2 SH2 domain-binding affinity

Zhen Dan Shi, Hongpeng Liu, Manchao Zhang, Karen M. Worthy, Lakshman Bindu, Dajun Yang, Robert J. Fisher, Terrence R. Burke

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

Although considerable effort has been devoted to developing Grb2 SH2 domain-binding antagonists, important questions related to ligand specificity, and identification of intracellular targets remain unanswered. In order to begin addressing these issues, the design, synthesis, and evaluation of a novel biotinylated macrocycle are reported that bears biotin functionality at a C-terminal rather than the traditional N-terminal position. With a Grb2 SH2 domain-binding K_eq value of 3.4 nM, the title macrocycle (5) is among the most potent biotinylated SH2 domain-binding ligands yet disclosed. This should be a useful tool for elucidating physiological targets of certain Grb2 SH2 domain-binding antagonists.

Original language	English (US)
Pages (from-to)	4200-4208
Number of pages	9
Journal	Bioorganic and Medicinal Chemistry
Volume	13
Issue number	13
DOIs	https://doi.org/10.1016/j.bmc.2005.04.028
State	Published - Jul 1 2005

Keywords

Biotin conjugate
Grb2 SH2 Domain
Macrocycle

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmc.2005.04.028

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title = "Synthesis of a C-terminally biotinylated macrocyclic peptide mimetic exhibiting high Grb2 SH2 domain-binding affinity",

abstract = "Although considerable effort has been devoted to developing Grb2 SH2 domain-binding antagonists, important questions related to ligand specificity, and identification of intracellular targets remain unanswered. In order to begin addressing these issues, the design, synthesis, and evaluation of a novel biotinylated macrocycle are reported that bears biotin functionality at a C-terminal rather than the traditional N-terminal position. With a Grb2 SH2 domain-binding Keq value of 3.4 nM, the title macrocycle (5) is among the most potent biotinylated SH2 domain-binding ligands yet disclosed. This should be a useful tool for elucidating physiological targets of certain Grb2 SH2 domain-binding antagonists.",

keywords = "Biotin conjugate, Grb2 SH2 Domain, Macrocycle",

author = "Shi, {Zhen Dan} and Hongpeng Liu and Manchao Zhang and Worthy, {Karen M.} and Lakshman Bindu and Dajun Yang and Fisher, {Robert J.} and Burke, {Terrence R.}",

note = "Funding Information: One of the authors (D.Y.) expresses appreciation to the Susan G. Komen Breast Cancer Foundation for financial support.",

year = "2005",

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doi = "10.1016/j.bmc.2005.04.028",

language = "English (US)",

volume = "13",

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T1 - Synthesis of a C-terminally biotinylated macrocyclic peptide mimetic exhibiting high Grb2 SH2 domain-binding affinity

AU - Shi, Zhen Dan

AU - Liu, Hongpeng

AU - Zhang, Manchao

AU - Worthy, Karen M.

AU - Bindu, Lakshman

AU - Yang, Dajun

AU - Fisher, Robert J.

AU - Burke, Terrence R.

N1 - Funding Information: One of the authors (D.Y.) expresses appreciation to the Susan G. Komen Breast Cancer Foundation for financial support.

PY - 2005/7/1

Y1 - 2005/7/1

N2 - Although considerable effort has been devoted to developing Grb2 SH2 domain-binding antagonists, important questions related to ligand specificity, and identification of intracellular targets remain unanswered. In order to begin addressing these issues, the design, synthesis, and evaluation of a novel biotinylated macrocycle are reported that bears biotin functionality at a C-terminal rather than the traditional N-terminal position. With a Grb2 SH2 domain-binding Keq value of 3.4 nM, the title macrocycle (5) is among the most potent biotinylated SH2 domain-binding ligands yet disclosed. This should be a useful tool for elucidating physiological targets of certain Grb2 SH2 domain-binding antagonists.

AB - Although considerable effort has been devoted to developing Grb2 SH2 domain-binding antagonists, important questions related to ligand specificity, and identification of intracellular targets remain unanswered. In order to begin addressing these issues, the design, synthesis, and evaluation of a novel biotinylated macrocycle are reported that bears biotin functionality at a C-terminal rather than the traditional N-terminal position. With a Grb2 SH2 domain-binding Keq value of 3.4 nM, the title macrocycle (5) is among the most potent biotinylated SH2 domain-binding ligands yet disclosed. This should be a useful tool for elucidating physiological targets of certain Grb2 SH2 domain-binding antagonists.

KW - Biotin conjugate

KW - Grb2 SH2 Domain

KW - Macrocycle

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SN - 0968-0896

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JO - Bioorganic and Medicinal Chemistry

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ER -

Synthesis of a C-terminally biotinylated macrocyclic peptide mimetic exhibiting high Grb2 SH2 domain-binding affinity

Abstract

Keywords

ASJC Scopus subject areas

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