Synthesis of cell-permeable stapled peptide dual inhibitors of the p53-Mdm2/Mdmx interactions via photoinduced cycloaddition

Michael M. Madden; Avinash Muppidi; Zhenyu Li; Xiaolong Li; Jiandong Chen; Qing Lin

doi:10.1016/j.bmcl.2011.01.004

Synthesis of cell-permeable stapled peptide dual inhibitors of the p53-Mdm2/Mdmx interactions via photoinduced cycloaddition

Michael M. Madden
, Avinash Muppidi
, Zhenyu Li
, Xiaolong Li
, Jiandong Chen
, Qing Lin

Chemistry

SUNY Buffalo
Moffitt Cancer Center

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

99 Scopus citations

Abstract

We report the first application of a photoinduced 1,3-dipolar cycloaddition reaction to 'staple' a peptide dual inhibitor of the p53-Mdm2/Mdmx interactions. A series of stapled peptide inhibitors were efficiently synthesized and showed excellent dual inhibitory activity in ELISA assay. Furthermore, the positively charged, stapled peptides showed enhanced cellular uptake along with modest in vivo activity.

Original language	English
Pages (from-to)	1472-1475
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	21
Issue number	5
DOIs	https://doi.org/10.1016/j.bmcl.2011.01.004
State	Published - Mar 1 2011

Keywords

Cellular uptake
Dipolar cycloaddition
Inhibitors
Protein-protein interaction
Stapled peptides

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10.1016/j.bmcl.2011.01.004

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title = "Synthesis of cell-permeable stapled peptide dual inhibitors of the p53-Mdm2/Mdmx interactions via photoinduced cycloaddition",

abstract = "We report the first application of a photoinduced 1,3-dipolar cycloaddition reaction to 'staple' a peptide dual inhibitor of the p53-Mdm2/Mdmx interactions. A series of stapled peptide inhibitors were efficiently synthesized and showed excellent dual inhibitory activity in ELISA assay. Furthermore, the positively charged, stapled peptides showed enhanced cellular uptake along with modest in vivo activity.",

keywords = "Cellular uptake, Dipolar cycloaddition, Inhibitors, Protein-protein interaction, Stapled peptides",

author = "Madden, \{Michael M.\} and Avinash Muppidi and Zhenyu Li and Xiaolong Li and Jiandong Chen and Qing Lin",

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AU - Madden, Michael M.

AU - Muppidi, Avinash

AU - Li, Zhenyu

AU - Li, Xiaolong

AU - Chen, Jiandong

AU - Lin, Qing

PY - 2011/3/1

Y1 - 2011/3/1

N2 - We report the first application of a photoinduced 1,3-dipolar cycloaddition reaction to 'staple' a peptide dual inhibitor of the p53-Mdm2/Mdmx interactions. A series of stapled peptide inhibitors were efficiently synthesized and showed excellent dual inhibitory activity in ELISA assay. Furthermore, the positively charged, stapled peptides showed enhanced cellular uptake along with modest in vivo activity.

AB - We report the first application of a photoinduced 1,3-dipolar cycloaddition reaction to 'staple' a peptide dual inhibitor of the p53-Mdm2/Mdmx interactions. A series of stapled peptide inhibitors were efficiently synthesized and showed excellent dual inhibitory activity in ELISA assay. Furthermore, the positively charged, stapled peptides showed enhanced cellular uptake along with modest in vivo activity.

KW - Cellular uptake

KW - Dipolar cycloaddition

KW - Inhibitors

KW - Protein-protein interaction

KW - Stapled peptides

UR - https://www.scopus.com/pages/publications/79951723092

U2 - 10.1016/j.bmcl.2011.01.004

DO - 10.1016/j.bmcl.2011.01.004

M3 - Article

C2 - 21277201

AN - SCOPUS:79951723092

SN - 0960-894X

VL - 21

SP - 1472

EP - 1475

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 5

ER -

Synthesis of cell-permeable stapled peptide dual inhibitors of the p53-Mdm2/Mdmx interactions via photoinduced cycloaddition

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Keywords

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