180977-31-5Relevant academic research and scientific papers
Intramolecular staudinger ligation towards biaryl-containing lactams
Masson, Geraldine,Den Hartog, Tim,Schoemaker, Hans E.,Hiemstra, Henk,Van Maarseveen, Jan H.
, p. 865 - 868 (2007/10/03)
Both 15- and 16-membered biaryl-type lactams were prepared in good yield using the intramolecular Staudinger ligation strategy. Georg Thieme Verlag Stuttgart.
Design and synthesis of non-peptide Ras CAAX mimetics as potent farnesyltransferase inhibitors
Qian, Yimin,Vogt, Andreas,Sebti, Sa?d M.,Hamilton, Andrew D.
, p. 217 - 223 (2007/10/03)
Cysteine farnesylation of the ras oncogene product Ras is required for its transforming activity and is catalyzed by farnesyltransferase (FTase). The Ras carboxyl terminal tetrapeptide CAAX (C is cysteine, A is any aliphatic amino acid, X is methionine or serine) is the minimum sequence for FTase recognition. We report here the design, synthesis, and biological characterization of Ras CAAX non-peptide mimetics in which the cysteine is linked through a reduced pseudopeptide bond to 4-amino-3'-carboxybiphenyl. These non-peptide mimetics are potent inhibitors of FTase (IC50 = 40 nM for the most potent inhibitor) and are highly selective for FTase over GGTase I (geranylgeranyltransferase I). They are not substrates for farnesylation, do not have peptidic features, and have no hydrolyzable bonds. Structure- activity studies reveal the importance of the position of the carboxylic acid on the aryl ring as well as the reduction of the cysteine amide bond. Substitution at the 2-position of 4-amino-3'-carboxybiphenyl increases inhibitory potency, while the removal of the carboxylic acid results in a 10- fold loss of inhibitory activity.
