Synthesis, Enzymatic Peptide Incorporation, and Applications of Diazirine-Containing Isoprenoid Diphosphate Analogues

Katarzyna Justyna; Riki Das; Ellen L. Lorimer; Jiayue Hu; Jodi S. Pedersen; Andrea M. Sprague-Getsy; Garrett L. Schey; Michelle A. Sieburg; Olivia J. Koehn; Yen Chih Wang; Yong Xiang Chen; James L. Hougland; Carol L. Williams; Mark D. Distefano

doi:10.1021/acs.orglett.3c02736

Synthesis, Enzymatic Peptide Incorporation, and Applications of Diazirine-Containing Isoprenoid Diphosphate Analogues

Katarzyna Justyna, Riki Das, Ellen L. Lorimer, Jiayue Hu, Jodi S. Pedersen, Andrea M. Sprague-Getsy, Garrett L. Schey, Michelle A. Sieburg, Olivia J. Koehn, Yen Chih Wang, Yong Xiang Chen, James L. Hougland, Carol L. Williams, Mark D. Distefano

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2 Scopus citations

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.

Original language	English (US)
Pages (from-to)	6767-6772
Number of pages	6
Journal	Organic Letters
Volume	25
Issue number	36
DOIs	https://doi.org/10.1021/acs.orglett.3c02736
State	Published - Sep 15 2023

ASJC Scopus subject areas

Biochemistry
Physical and Theoretical Chemistry
Organic Chemistry

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Justyna, K., Das, R., Lorimer, E. L., Hu, J., Pedersen, J. S., Sprague-Getsy, A. M., Schey, G. L., Sieburg, M. A., Koehn, O. J., Wang, Y. C., Chen, Y. X., Hougland, J. L., Williams, C. L., & Distefano, M. D. (2023). Synthesis, Enzymatic Peptide Incorporation, and Applications of Diazirine-Containing Isoprenoid Diphosphate Analogues. Organic Letters, 25(36), 6767-6772. https://doi.org/10.1021/acs.orglett.3c02736

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 2023, 'Synthesis, Enzymatic Peptide Incorporation, and Applications of Diazirine-Containing Isoprenoid Diphosphate Analogues', Organic Letters, vol. 25, no. 36, pp. 6767-6772. https://doi.org/10.1021/acs.orglett.3c02736

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title = "Synthesis, Enzymatic Peptide Incorporation, and Applications of Diazirine-Containing Isoprenoid Diphosphate Analogues",

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 = "Katarzyna Justyna and Riki Das and Lorimer, {Ellen L.} and Jiayue Hu and Pedersen, {Jodi S.} and Sprague-Getsy, {Andrea M.} and Schey, {Garrett L.} and Sieburg, {Michelle A.} and Koehn, {Olivia J.} and Wang, {Yen Chih} and Chen, {Yong Xiang} and Hougland, {James L.} and Williams, {Carol L.} and Distefano, {Mark D.}",

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T1 - Synthesis, Enzymatic Peptide Incorporation, and Applications of Diazirine-Containing Isoprenoid Diphosphate Analogues

AU - Justyna, Katarzyna

AU - Das, Riki

AU - Lorimer, Ellen L.

AU - Hu, Jiayue

AU - Pedersen, Jodi S.

AU - Sprague-Getsy, Andrea M.

AU - Schey, Garrett L.

AU - Sieburg, Michelle A.

AU - Koehn, Olivia J.

AU - Wang, Yen Chih

AU - Chen, Yong Xiang

AU - Hougland, James L.

AU - Williams, Carol L.

AU - Distefano, Mark D.

PY - 2023/9/15

Y1 - 2023/9/15

N2 - 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.

AB - 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.

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Synthesis, Enzymatic Peptide Incorporation, and Applications of Diazirine-Containing Isoprenoid Diphosphate Analogues

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