Carbocyclic Puromycin: Synthesis and Inhibition of Protein Biosynthesis

Robert Vince, Susan Daluge, Jay Brownell

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20 Scopus citations

Abstract

The carbocyclic analogue of puromycin was prepared by the coupling of N-(benzyloxycarbonyl)-p-methoxy-L-phenylalanine to the racemic aminonucleoside (±)-9-[3β-amino-2β-hydroxy-4a-(hydroxymethyl)cyclopent-la-yl] -6- (dimethylamino)purine, followed by separation of the diastereomers and subsequent removal of the Cbz blocking group. Kinetic studies indicate that carbocyclic puromycin is an excellent substrate for the peptidyltransferase reaction with both prokaryotic and eukaryotic ribosomes. A comparison of carbocyclic puromycin with previously synthesized analogues indicate that the furanosyl ring oxygen and the hydroxymethyl group of puromycin do not contribute to ribosomal binding, but both moieties contribute to the rate of product formation from the enzyme-substrate complex. Carbocyclic puromycin was equal to puromycin when evaluated for cytotoxicity using P-388 mouse lymphoid leukemia cells in culture.

Original languageEnglish (US)
Pages (from-to)2400-2403
Number of pages4
JournalJournal of medicinal chemistry
Volume29
Issue number11
DOIs
StatePublished - 1986

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