Linked Life Data

19894725

Source:http://linkedlifedata.com/resource/pubmed/id/19894725

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2009-12-17
pubmed:abstractText
Rab geranylgeranyl transferase (RabGGTase) catalyzes the attachment of geranylgeranyl isoprenoids to Rab guanine triphosphatases, which are key regulators in vesicular transport. Because geranylgeranylation is required for proper function and overexpression of Rabs has been observed in various cancers, RabGGTase may be a target for novel therapeutics. The development of selective inhibitors is, however, difficult because two related enzymes involved in other cellular processes exist in eukaryotes and because RabGGTase recognizes protein substrates indirectly, resulting in relaxed specificity. We report the synthesis of a peptidic library based on the farnesyl transferase inhibitor pepticinnamin E. Of 469 compounds investigated, several were identified as selective for RabGGTase with low micromolar IC(50) values. The compounds were not generally cytotoxic and inhibited Rab isoprenylation in COS-7 cells. Crystal structure analysis revealed that selective inhibitors interact with a tunnel unique to RabGGTase, implying that this structural motif is an attractive target for improved RabGGTase inhibitors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1520-4804
pubmed:author
pubmed:issnType
Electronic
pubmed:day
24
pubmed:volume
52
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8025-37
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Design, synthesis, and characterization of peptide-based rab geranylgeranyl transferase inhibitors.
pubmed:affiliation
Department of Chemical Biology, Biochemistry, Max Planck Institute of Molecular Physiology,Otto-Hahn-Strassse 11, 44227 Dortmund, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't