Helical beta-peptide inhibitors of the p53-hDM2 interaction.

Helical beta-peptide inhibitors of the p53-hDM2 interaction. Research Abstract Details 

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Helical beta-peptide inhibitors of the p53-hDM2 interaction. Abstract Text:

Joshua A Kritzer,James D Lear,Michael E Hodsdon,Alanna Schepartz,

hDM2 is recognized in vivo by a short alpha-helix within the p53 trans-activation domain (p53AD). Disruption of the p53.hDM2 interaction is an important goal for cancer therapy. A functional epitope comprised of three residues on one face of the p53AD helix (F19, W23, and L26) contributes heavily to the binding free energy. We hypothesized that the p53AD functional epitope would be recapitulated if the side chains of F19, W23, and L26 were presented at successive positions three residues apart on a stabilized beta3-peptide 14-helix. Here, we report a set of beta3-peptides that possess significant 14-helix structure in water; one recognizes a cleft on the surface of hDM2 with nanomolar affinity. The strategy for beta3-peptide design that we describe is general and may have advantages over one in which individual or multiple beta-amino acid substitutions are introduced into a functional alpha-peptide, because it is based on homology at the level of secondary structure, not primary sequence.

Helical beta-peptide inhibitors of the p53-hDM2 interaction. Publishing Authors By Initials

JA Kritzer,JD Lear,ME Hodsdon,A Schepartz,

For similar proteins: dna-binding proteins: tumor suppressor protein p53 research abstracts see: proteins: dna-binding proteins: tumor suppressor protein p53 research

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Helical beta-peptide inhibitors of the p53-hDM2 interaction. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Journal of the American Chemical Society

VOLUME: 126

Page Numbers: 9468-9

Journal Abbreviation: J. Am. Chem. Soc.

ISSN: 0002-7863

DAY: 11

MONTH: Aug

YEAR: 2004

Helical beta-peptide inhibitors of the p53-hDM2 interaction. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7503056

Helical beta-peptide inhibitors of the p53-hDM2 interaction. Keywords Mesh Terms:

KEYWORDS: Tumor Suppressor Protein p53

MESH TERMS: metabolism

Chemical & Substance for Abstract: Helical beta-peptide inhibitors of the p53-hDM2 interaction. Information

Substance Name: Proto-Oncogene Proteins c-mdm2

Registry Number: EC 6.3.2.19

Grant and Affiliation Information for Helical beta-peptide inhibitors of the p53-hDM2 interaction.

AFFILIATION: Department of Chemistry, Yale University, New Haven, Connecticut 06520, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM65453

ACRONYM: GM

MEDLINETA: J Am Chem Soc

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