Solution structure of a beta-peptide ligand for hDM2.

Solution structure of a beta-peptide ligand for hDM2. Research Abstract Details 

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Solution structure of a beta-peptide ligand for hDM2. Abstract Text:

Joshua A Kritzer,Michael E Hodsdon,Alanna Schepartz,

We recently reported a beta-peptide foldamer, beta53-1, that folds into a 14-helix in aqueous solution, binds the oncoprotein hDM2 with submicromolar affinity, and potently inhibits the interaction of hDM2 with a peptide derived from the activation domain of p53 (p53AD). Here, we present the solution structure of beta53-1 in methanol. Details of the structure illustrate fundamental and novel elements of beta-peptide folding and recognition. These elements include the detailed arrangement of a complex, 14-helix-stabilizing salt bridge on one helical face, and a unique "wedge into cleft" packing interaction along a second. The structure also reveals how a subtle distortion in the beta53-1 14-helix geometry alters the presentation of its recognition epitope, rendering it particularly well suited for alpha-helix mimicry. The solution structure of beta53-1 demonstrates that well folded beta-peptide oligomers can effectively present an extended, highly variable surface that could be used as a general platform for targeting critical protein-protein interfaces.

Solution structure of a beta-peptide ligand for hDM2. Publishing Authors By Initials

JA Kritzer,ME Hodsdon,A Schepartz,

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Solution structure of a beta-peptide ligand for hDM2. Journal Published:

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

Journal: Journal of the American Chemical Society

VOLUME: 127

Page Numbers: 4118-9

Journal Abbreviation: J. Am. Chem. Soc.

ISSN: 0002-7863

DAY: 30

MONTH: Mar

YEAR: 2005

Solution structure of a beta-peptide ligand for hDM2. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7503056

Solution structure of a beta-peptide ligand for hDM2. Keywords Mesh Terms:

KEYWORDS: Solutions

MESH TERMS: metabolism

Chemical & Substance for Abstract: Solution structure of a beta-peptide ligand for hDM2. Information

Substance Name: Proto-Oncogene Proteins c-mdm2

Registry Number: EC 6.3.2.19

Grant and Affiliation Information for Solution structure of a beta-peptide ligand for hDM2.

AFFILIATION: Department of Chemistry, Yale University, New Haven, Connecticut 06510, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM 59843

ACRONYM: GM

MEDLINETA: J Am Chem Soc

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