Synthesis and evaluation of benzophenone-based photoaffinity labeling analogs of prenyl pyrophosphates containing stable amide linkages

Tammy C. Turek; Igor Gaon; Dave Gamache; Mark D. Distefano

doi:10.1016/S0960-894X(97)00373-9

Synthesis and evaluation of benzophenone-based photoaffinity labeling analogs of prenyl pyrophosphates containing stable amide linkages

Tammy C. Turek, Igor Gaon, Dave Gamache, Mark D. Distefano

Chemistry (Twin Cities)

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

31 Scopus citations

Abstract

The syntheses of two photoactive prenyl pyrophosphate analogs (1a and 1b) that incorporate stable amide-linked benzophenones are described. Compound 1a contains a single isoprene (C₅) unit between the phyophosphate and benzophenone functionalities while 1b contains a geranyl (C₁₀) moiety. Compounds 1a and 1b are competitive inhibitors of yeast farnesyl protein transferase with respect to farnesyl pyrophosphate and have K(I) values of 6000 nM. and 700 nM. Upon irradiation [³²P]-1b preferentially labels the β-subunits of yeast farnesyl protein transferase and human geranylgeranyl protein transferase.

Original language	English (US)
Pages (from-to)	2125-2130
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	7
Issue number	16
DOIs	https://doi.org/10.1016/S0960-894X(97)00373-9
State	Published - Aug 19 1997

Bibliographical note

Funding Information:
Acknowledgements. This research was supported by funds from the American Cancer Society (BE-222, IN-13-33-47, and JFRA-584). We thank C. D. Poulter for providing E. coli DH5oJpGP114 and C. A. Omer for providing E. coli BL21(DE3)/pRD578. The structure of 6a was determined by Dr. V. G. Young, Jr. in the x-ray crystallographic laboratory in the Department of Chemistry at the University of Minnesota.

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title = "Synthesis and evaluation of benzophenone-based photoaffinity labeling analogs of prenyl pyrophosphates containing stable amide linkages",

abstract = "The syntheses of two photoactive prenyl pyrophosphate analogs (1a and 1b) that incorporate stable amide-linked benzophenones are described. Compound 1a contains a single isoprene (C5) unit between the phyophosphate and benzophenone functionalities while 1b contains a geranyl (C10) moiety. Compounds 1a and 1b are competitive inhibitors of yeast farnesyl protein transferase with respect to farnesyl pyrophosphate and have K(I) values of 6000 nM. and 700 nM. Upon irradiation [32P]-1b preferentially labels the β-subunits of yeast farnesyl protein transferase and human geranylgeranyl protein transferase.",

author = "Turek, {Tammy C.} and Igor Gaon and Dave Gamache and Distefano, {Mark D.}",

note = "Funding Information: Acknowledgements. This research was supported by funds from the American Cancer Society (BE-222, IN-13-33-47, and JFRA-584). We thank C. D. Poulter for providing E. coli DH5oJpGP114 and C. A. Omer for providing E. coli BL21(DE3)/pRD578. The structure of 6a was determined by Dr. V. G. Young, Jr. in the x-ray crystallographic laboratory in the Department of Chemistry at the University of Minnesota.",

year = "1997",

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doi = "10.1016/S0960-894X(97)00373-9",

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T1 - Synthesis and evaluation of benzophenone-based photoaffinity labeling analogs of prenyl pyrophosphates containing stable amide linkages

AU - Turek, Tammy C.

AU - Gaon, Igor

AU - Gamache, Dave

AU - Distefano, Mark D.

N1 - Funding Information: Acknowledgements. This research was supported by funds from the American Cancer Society (BE-222, IN-13-33-47, and JFRA-584). We thank C. D. Poulter for providing E. coli DH5oJpGP114 and C. A. Omer for providing E. coli BL21(DE3)/pRD578. The structure of 6a was determined by Dr. V. G. Young, Jr. in the x-ray crystallographic laboratory in the Department of Chemistry at the University of Minnesota.

PY - 1997/8/19

Y1 - 1997/8/19

N2 - The syntheses of two photoactive prenyl pyrophosphate analogs (1a and 1b) that incorporate stable amide-linked benzophenones are described. Compound 1a contains a single isoprene (C5) unit between the phyophosphate and benzophenone functionalities while 1b contains a geranyl (C10) moiety. Compounds 1a and 1b are competitive inhibitors of yeast farnesyl protein transferase with respect to farnesyl pyrophosphate and have K(I) values of 6000 nM. and 700 nM. Upon irradiation [32P]-1b preferentially labels the β-subunits of yeast farnesyl protein transferase and human geranylgeranyl protein transferase.

AB - The syntheses of two photoactive prenyl pyrophosphate analogs (1a and 1b) that incorporate stable amide-linked benzophenones are described. Compound 1a contains a single isoprene (C5) unit between the phyophosphate and benzophenone functionalities while 1b contains a geranyl (C10) moiety. Compounds 1a and 1b are competitive inhibitors of yeast farnesyl protein transferase with respect to farnesyl pyrophosphate and have K(I) values of 6000 nM. and 700 nM. Upon irradiation [32P]-1b preferentially labels the β-subunits of yeast farnesyl protein transferase and human geranylgeranyl protein transferase.

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VL - 7

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JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 16

ER -

Synthesis and evaluation of benzophenone-based photoaffinity labeling analogs of prenyl pyrophosphates containing stable amide linkages

Abstract

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