Farnesyl Diphosphate Analogues with Omega-bioorthogonal Azide and Alkyne Functional Groups for Protein Farnesyl Transferase-catalyzed Ligation Reactions

Overview

Journal J Org Chem

Publisher American Chemical Society

Specialty Chemistry

Date 2007 Nov 6

PMID 17979291

Citations 29

Authors

Guillermo R Labadie

Rajesh Viswanathan

C Dale Poulter

Affiliations

Soon will be listed here.

Abstract

Eleven farnesyl diphosphate analogues, which contained omega-azide or alkyne substituents suitable for bioorthogonal Staudinger and Huisgen [3 + 2] cycloaddition coupling reactions, were synthesized. The analogues were evaluated as substrates for the alkylation of peptide cosubstrates by yeast protein farnesyl transferase. Five of the diphosphates were good alternative substrates for farnesyl diphosphate (FPP). Steady-state kinetic constants were measured for the active compounds, and the products were characterized by HPLC and LC-MS. Two of the analogues gave steady-state kinetic parameters (kcat and Km) very similar to those of the natural substrate.

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