Conformationally homogeneous cyclic tetrapeptides: useful new three-dimensional scaffolds.

Conformationally homogeneous cyclic tetrapeptides: useful new three-dimensional scaffolds. Research Abstract Details 

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Conformationally homogeneous cyclic tetrapeptides: useful new three-dimensional scaffolds. Abstract Text:

Matthew P Glenn,Michael J Kelso,Joel D A Tyndall,David P Fairlie,

The most commonly recognized motifs in protein-protein interactions are gamma and beta turns, which are defined by three to four contiguous amino acids in a peptide sequence. Cyclic tetrapeptides thus represent minimalist turn mimetics, but their usefulness is compromised by strain in their 12-membered rings, making them difficult to cyclize, unstable to hydrolysis/metabolism, and conformationally heterogeneous in polar solvents. Appropriate placement of a beta amino acid in a tetrapeptide creates a 13-membered ring that is shown to be easier to cyclize, hydrolytically more stable, and conformationally homogeneous in polar solvents such as DMSO and water. Three-dimensional structures reveal that these cyclic tetrapeptides are novel rigid scaffolds, their unique side-chain projections matching a structurally diverse range of useful nonpeptidic templates, including sugars and spirocyclic compounds, found as components of natural products. The results provide a potentially useful link between protein architecture and organic natural products. On the basis of protein turn sequences (not protein structures) alone simple cyclic tetrapeptide libraries with a beta amino acid can be rationally designed as conformationally restricted, easily synthesized, and stereochemically controlled screening tools for rapidly identifying pharmacophore space that can then be computer-matched to more complex known natural product templates for drug development.

Conformationally homogeneous cyclic tetrapeptides: useful new three-dimensional scaffolds. Publishing Authors By Initials

MP Glenn,MJ Kelso,JD Tyndall,DP Fairlie,

For similar natural sciences: physics: thermodynamics research abstracts see: natural sciences: physics: thermodynamics research

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Conformationally homogeneous cyclic tetrapeptides: useful new three-dimensional scaffolds. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of the American Chemical Society

VOLUME: 125

Page Numbers: 640-1

Journal Abbreviation: J. Am. Chem. Soc.

ISSN: 0002-7863

DAY: 22

MONTH: Jan

YEAR: 2003

Conformationally homogeneous cyclic tetrapeptides: useful new three-dimensional scaffolds. Information

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LANGUAGE: eng

NlmUniqueID: 7503056

Conformationally homogeneous cyclic tetrapeptides: useful new three-dimensional scaffolds. Keywords Mesh Terms:

KEYWORDS: Thermodynamics

MESH TERMS: chemistry

Chemical & Substance for Abstract: Conformationally homogeneous cyclic tetrapeptides: useful new three-dimensional scaffolds. Information

Substance Name: 2-amino-4-phenylbutyric acid

Registry Number: 7636-28-4

Grant and Affiliation Information for Conformationally homogeneous cyclic tetrapeptides: useful new three-dimensional scaffolds.

AFFILIATION: Centre for Drug Design and Development, Institute for Molecular Bioscience, University of Queensland, Brisbane Qld 4072, Australia.

Country: United States

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MEDLINETA: J Am Chem Soc

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