Inhibition of peptidyltransferase and possible mode of action of a dipeptidyl chloramphenicol analog

Sara C. McFarlan; Robert Vince

doi:10.1016/S0006-291X(84)80097-2

Inhibition of peptidyltransferase and possible mode of action of a dipeptidyl chloramphenicol analog

Sara C. McFarlan, Robert Vince

Center for Drug Design

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

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Abstract

A dipeptidyl chloramphenicol analog, D-threo-2-(L-phenylalanylglycyl)amino-3-p-nitrophenyl-1,3-propanediol, has been prepared and examined as an inhibitor of ribosomal peptidyltransferase. The analog is a more effective inhibitor of poly (U,C) directed protein biosynthesis in an Escherichia coli cell-free system than chloramphenicol and shows inhibitory activity equal to the parent antibiotic in the transpeptidation reaction. These results and the common structural features of puromycin and this compound suggest a model for the binding modes of chloramphenicol and chloramphenicol analogs. This proposal invokes four major binding pockets at the A-site of the peptidyltransferase center.

Original language	English (US)
Pages (from-to)	748-754
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	122
Issue number	2
DOIs	https://doi.org/10.1016/S0006-291X(84)80097-2
State	Published - Jul 31 1984

Bibliographical note

Funding Information:
We thank Jay Br ownell for assistance in the biological assays. This investigation was supported by Grants CA 13592 and CA 23263 from the National Cancer Institute, Department of Health, Education, and Welfare.

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abstract = "A dipeptidyl chloramphenicol analog, D-threo-2-(L-phenylalanylglycyl)amino-3-p-nitrophenyl-1,3-propanediol, has been prepared and examined as an inhibitor of ribosomal peptidyltransferase. The analog is a more effective inhibitor of poly (U,C) directed protein biosynthesis in an Escherichia coli cell-free system than chloramphenicol and shows inhibitory activity equal to the parent antibiotic in the transpeptidation reaction. These results and the common structural features of puromycin and this compound suggest a model for the binding modes of chloramphenicol and chloramphenicol analogs. This proposal invokes four major binding pockets at the A-site of the peptidyltransferase center.",

author = "McFarlan, {Sara C.} and Robert Vince",

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AU - McFarlan, Sara C.

AU - Vince, Robert

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N2 - A dipeptidyl chloramphenicol analog, D-threo-2-(L-phenylalanylglycyl)amino-3-p-nitrophenyl-1,3-propanediol, has been prepared and examined as an inhibitor of ribosomal peptidyltransferase. The analog is a more effective inhibitor of poly (U,C) directed protein biosynthesis in an Escherichia coli cell-free system than chloramphenicol and shows inhibitory activity equal to the parent antibiotic in the transpeptidation reaction. These results and the common structural features of puromycin and this compound suggest a model for the binding modes of chloramphenicol and chloramphenicol analogs. This proposal invokes four major binding pockets at the A-site of the peptidyltransferase center.

AB - A dipeptidyl chloramphenicol analog, D-threo-2-(L-phenylalanylglycyl)amino-3-p-nitrophenyl-1,3-propanediol, has been prepared and examined as an inhibitor of ribosomal peptidyltransferase. The analog is a more effective inhibitor of poly (U,C) directed protein biosynthesis in an Escherichia coli cell-free system than chloramphenicol and shows inhibitory activity equal to the parent antibiotic in the transpeptidation reaction. These results and the common structural features of puromycin and this compound suggest a model for the binding modes of chloramphenicol and chloramphenicol analogs. This proposal invokes four major binding pockets at the A-site of the peptidyltransferase center.

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Inhibition of peptidyltransferase and possible mode of action of a dipeptidyl chloramphenicol analog

Abstract

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