Design, synthesis, and evaluation of sugar amino acid based inhibitors of protein prenyl transferases PFT and PGGT-1
article
Eleven analogues of the C-terminal Ca1a2X motif found in natural substrates of the prenyl transferases PFT and PGGT-1 were synthesized and evaluated for their inhibition potency and selectivity against PFT and PGGT-1. Replacement of the central dipeptide part a1a 2 by a benzylated sugar amino acid resulted in a good and highly selective PFT inhibitor (8, IC50 = 250 ± 20 nM). The methyl ester of 8 (13) selectively inhibited protein farnesylation in cultured cells. Chemicals / CAS: Alkyl and Aryl Transferases, EC 2.5.-; Amino Acids; Farnesyltranstransferase, EC 2.5.1.29; geranylgeranyltransferase type-I, EC 2.5.1.-; Sugar Acids.
Topics
Biomedical Researchamino acid derivativebenzylated sugar amino acidenzyme inhibitorprotein farnesyltransferase inhibitorprotein geranylgeranyltransferase 1 inhibitortr 006unclassified drugamino acid substitutionarticlecarboxy terminal sequencedrug designdrug potencydrug selectivitydrug synthesisenzyme inhibitionenzyme substrateevaluationfarnesylationIC 50inhibition kineticsprotein motifreaction analysisAlkyl and Aryl TransferasesAmino AcidsAnimalsCell LineCHO CellsCricetinaeDrug DesignFarnesyltranstransferaseStructure-Activity RelationshipSugar Acids
TNO Identifier
237907
ISSN
00222623
Source
Journal of Medicinal Chemistry, 47(16), pp. 3920-3923.
Pages
3920-3923
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