Linked Life Data

12526657

Source:http://linkedlifedata.com/resource/pubmed/id/12526657

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-1-15
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0002-7863
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
125
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
640-1
pubmed:dateRevised
2008-1-17
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Conformationally homogeneous cyclic tetrapeptides: useful new three-dimensional scaffolds.
pubmed:affiliation
Centre for Drug Design and Development, Institute for Molecular Bioscience, University of Queensland, Brisbane Qld 4072, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't