Faculty Collaboration Database

Synthesis, Enzymatic Peptide Incorporation, and Applications of Diazirine-Containing Isoprenoid Diphosphate Analogues. Org Lett 2023 Sep 15;25(36):6767-6772

Date

09/05/2023

Pubmed ID

37669435

Pubmed Central ID

PMC10755972

DOI

10.1021/acs.orglett.3c02736

Scopus ID

2-s2.0-85171393145 (requires institutional sign-in at Scopus site)

Abstract

Prenylated proteins contain C₁₅ or C₂₀ isoprenoids linked to cysteine residues positioned near their C-termini. Here we describe the preparation of isoprenoid diphosphate analogues incorporating diazirine groups that can be used to probe interactions between prenylated proteins and other proteins that interact with them. Studies using synthetic peptides and whole proteins demonstrate that these diazirine analogues are efficient substrates for prenyltransferases. Photo-cross-linking experiments using peptides incorporating the diazirine-functionalized isoprenoids selectively cross-link to several different proteins. These new isoprenoid analogues should be broadly useful in the studies of protein prenylation.

Author List

Justyna K, Das R, Lorimer EL, Hu J, Pedersen JS, Sprague-Getsy AM, Schey GL, Sieburg MA, Koehn OJ, Wang YC, Chen YX, Hougland JL, Williams CL, Distefano MD

Authors

Olivia Koehn Postdoctoral Fellow in the Pharmacology and Toxicology department at Medical College of Wisconsin
Carol L. Williams PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cysteine
Diazomethane
Diphosphates
Peptides
Terpenes