Linked Life Data

10814193

Source:http://linkedlifedata.com/resource/pubmed/id/10814193

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2000-8-17
pubmed:abstractText
The posttranslational addition of a farnesyl moiety to the Ras oncoprotein is essential for its membrane localization and is required for both its biological activity and ability to induce malignant transformation. We describe the design and synthesis of a farnesyl pyrophosphate (FPP) analogue, 8-anilinogeranyl pyrophosphate 3 (AGPP), in which the omega-terminal isoprene unit of the farnesyl group has been replaced with an aniline functionality. The key steps in the synthesis are the reductive amination of the alpha,beta-unsaturated aldehyde 5 to form the lipid analogue 6, and the subsequent conversion of the allylic alcohol 7 to the chloride 8 via Ph(3)PCl(2) followed by displacement with [(n-Bu)(4)N](3)HP(2)O(7) to give AGPP (3). AGPP is a substrate for protein farnesyltransferase (FTase) and is transferred to Ras by FTase with the same kinetics as the natural substrate, FPP. AGPP is highly selective, showing little inhibitory activity against either geranylgeranyl-protein transferase type I (GGTase I) (K(i) = 0.06 microM, IC(50) = 20 microM) or squalene synthase (IC(50) = 1000 microM). AGPP is the first efficiently transferable analogue of FPP to be modified at the omega-terminus that provides a platform from which additional analogues can be made to probe the biological function of protein farnesylation. AGPP is the first example of a class of compounds that are alternate substrates for protein isoprenylation that are not inhibitors of squalene synthase.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-3263
pubmed:author
pubmed:issnType
Print
pubmed:day
19
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3027-33
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Design and synthesis of a transferable farnesyl pyrophosphate analogue to Ras by protein farnesyltransferase.
pubmed:affiliation
Department of Biochemistry, Kentucky Center for Structural Biology, University of Kentucky, Lexington, Kentucky 40536-0084, USA.
pubmed:publicationType
Journal Article