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1e26
From Proteopedia
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DESIGN, SYNTHESIS AND X-RAY CRYSTAL STRUCTURE OF A POTENT DUAL INHIBITOR OF THYMIDYLATE SYNTHASE AND DIHYDROFOLATE REDUCTASE AS AN ANTITUMOR AGENT.
Overview
A novel N- inverted question mark2-amino-4-methyl[(pyrrolo[2, 3-d]pyrimidin-5-yl)ethyl]benzoyl inverted question mark-L-glutamic acid, (3a) was designed and synthesized as a potent dual inhibitor of, thymidylate synthase (TS) and dihydrofolate reductase (DHFR) and as an, antitumor agent. Compound 3b, the N7-benzylated analogue of 3a, was also, synthesized as an antitumor agent. The synthesis of 3a was accomplished, via a 12-step sequence which involved the synthesis of, 2-amino-4-methylpyrrolo[2,3-d]pyrimidine (10) in 5 steps from, 2-acetylbutyrolactone. Protection of the 2-amino group of 10 and, regioselective iodination at the 5-position followed by, palladium-catalyzed coupling afforded intermediate 14 which was converted, to 3a by reduction and saponification. Similar synthetic ... [(full description)]
About this Structure
1E26 is a [Single protein] structure of sequence from [Pneumocystis carinii] with NAP and GPB as [ligands]. Active as [Dihydrofolate reductase], with EC number [1.5.1.3]. Structure known Active Site: S1. Full crystallographic information is available from [OCA].
Reference
Design, synthesis, and X-ray crystal structure of a potent dual inhibitor of thymidylate synthase and dihydrofolate reductase as an antitumor agent., Gangjee A, Yu J, McGuire JJ, Cody V, Galitsky N, Kisliuk RL, Queener SF, J Med Chem. 2000 Oct 19;43(21):3837-51. PMID:11052789
Page seeded by OCA on Tue Oct 30 12:35:46 2007
