Linked Life Data

15578931

Source:http://linkedlifedata.com/resource/pubmed/id/15578931

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2004-12-6
pubmed:abstractText
A novel strategy that targets protein for degradation has recently been developed by exploiting a protein-targeting chimeric molecule ('Protac'). Typically, the chimeric Protac is composed of a small-molecule ligand ('bait') on one end and a synthetic octapeptide on the other. This octapeptide is recognized by E3 ubiquitin ligase pVHL (von Hippel Lindau tumor suppressor protein), thereby recruiting a small molecule-bound protein ('prey') to pVHL for ubiquitination and degradation. Since selective degradation of a cellular protein generates a "loss of function" mutation, this protein knock-out strategy may be useful to study the function of a given protein or to evaluate whether a cellular protein is a potential target for drug intervention, in a manner reminiscent of gene knock-out or siRNA approaches. Herein, we show that a synthetic pentapeptide is sufficient to interact with pVHL E3 ligase, and that the pentapeptide-based Protac efficiently induces ubiquitination and degradation of target protein. Our results also demonstrate that the pentapeptide-based Protac can enter cells efficiently to exerts its biological activity effectively. These results suggest that the synthetic pentapeptide can be used either directly in the preparation of cell-permeable Protacs or as a template to develop peptidomimetic or non-peptide Protacs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1386-2073
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
689-97
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Targeted degradation of proteins by small molecules: a novel tool for functional proteomics.
pubmed:affiliation
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 907 Rose Street, Lexington, Kentucky 40536, USA
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't