Synthesis of a-factor peptide from Saccharomyces cerevisiae and photoactive analogues via Fmoc solid phase methodology

Daniel G. Mullen; Kelly Kyro; Melinda Hauser; Martin Gustavsson; Gianluigi Veglia; Jeffery M. Becker; Fred Naider; Mark D. Distefano

doi:10.1016/j.bmc.2010.11.006

Synthesis of a-factor peptide from Saccharomyces cerevisiae and photoactive analogues via Fmoc solid phase methodology

Daniel G. Mullen, Kelly Kyro, Melinda Hauser, Martin Gustavsson, Gianluigi Veglia, Jeffery M. Becker, Fred Naider, Mark D. Distefano

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

a-Factor from Saccharomyces cerevisiae is a farnesylated dodecapeptide involved in mating. The molecule binds to a G-protein coupled receptor and hence serves as a simple system for studying the interactions between prenylated molecules and their cognate receptors. Here, we describe the preparation of a-factor and two photoactive analogues via Fmoc solid-phase peptide synthesis using hydrazinobenzoyl AM NovaGel™ resin; the structure of the synthetic a-factor was confirmed by MS-MS analysis and NMR; the structures of the analogues were confirmed by MS-MS analysis. Using a yeast growth arrest assay, the analogues were found to have activity comparable to a-factor itself.

Original language	English (US)
Pages (from-to)	490-497
Number of pages	8
Journal	Bioorganic and Medicinal Chemistry
Volume	19
Issue number	1
DOIs	https://doi.org/10.1016/j.bmc.2010.11.006
State	Published - Jan 1 2011

Bibliographical note

Funding Information:
The authors thank Bruce Witthuhn at University of Minnesota Center for Mass Spectrometry and Proteomics for assistance in performing the mass spectrometry experiments. This research was supported by the National Institutes of Health Grants GM58442 (M.D.D.) and GM22087 (J.M.B.).

Keywords

Benzophenone
C-Terminal methyl ester
Farnesyl
Peptide synthesis
Photoaffinity labeling
Prenylation
a-Factor

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abstract = "a-Factor from Saccharomyces cerevisiae is a farnesylated dodecapeptide involved in mating. The molecule binds to a G-protein coupled receptor and hence serves as a simple system for studying the interactions between prenylated molecules and their cognate receptors. Here, we describe the preparation of a-factor and two photoactive analogues via Fmoc solid-phase peptide synthesis using hydrazinobenzoyl AM NovaGel{\texttrademark} resin; the structure of the synthetic a-factor was confirmed by MS-MS analysis and NMR; the structures of the analogues were confirmed by MS-MS analysis. Using a yeast growth arrest assay, the analogues were found to have activity comparable to a-factor itself.",

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AU - Mullen, Daniel G.

AU - Kyro, Kelly

AU - Hauser, Melinda

AU - Gustavsson, Martin

AU - Veglia, Gianluigi

AU - Becker, Jeffery M.

AU - Naider, Fred

AU - Distefano, Mark D.

N1 - Funding Information: The authors thank Bruce Witthuhn at University of Minnesota Center for Mass Spectrometry and Proteomics for assistance in performing the mass spectrometry experiments. This research was supported by the National Institutes of Health Grants GM58442 (M.D.D.) and GM22087 (J.M.B.).

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N2 - a-Factor from Saccharomyces cerevisiae is a farnesylated dodecapeptide involved in mating. The molecule binds to a G-protein coupled receptor and hence serves as a simple system for studying the interactions between prenylated molecules and their cognate receptors. Here, we describe the preparation of a-factor and two photoactive analogues via Fmoc solid-phase peptide synthesis using hydrazinobenzoyl AM NovaGel™ resin; the structure of the synthetic a-factor was confirmed by MS-MS analysis and NMR; the structures of the analogues were confirmed by MS-MS analysis. Using a yeast growth arrest assay, the analogues were found to have activity comparable to a-factor itself.

AB - a-Factor from Saccharomyces cerevisiae is a farnesylated dodecapeptide involved in mating. The molecule binds to a G-protein coupled receptor and hence serves as a simple system for studying the interactions between prenylated molecules and their cognate receptors. Here, we describe the preparation of a-factor and two photoactive analogues via Fmoc solid-phase peptide synthesis using hydrazinobenzoyl AM NovaGel™ resin; the structure of the synthetic a-factor was confirmed by MS-MS analysis and NMR; the structures of the analogues were confirmed by MS-MS analysis. Using a yeast growth arrest assay, the analogues were found to have activity comparable to a-factor itself.

KW - Benzophenone

KW - C-Terminal methyl ester

KW - Farnesyl

KW - Peptide synthesis

KW - Photoaffinity labeling

KW - Prenylation

KW - a-Factor

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Synthesis of a-factor peptide from Saccharomyces cerevisiae and photoactive analogues via Fmoc solid phase methodology

Abstract

Bibliographical note

Keywords

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