An active puromycin analog derived from a non-nephrotoxic aminonucleoside

Robert Vince; Ronald G. Almquist; Clare L. Ritter; Frances N. Shirota; Herbert T. Nagasawa

doi:10.1016/0024-3205(76)90063-1

An active puromycin analog derived from a non-nephrotoxic aminonucleoside

Robert Vince, Ronald G. Almquist, Clare L. Ritter, Frances N. Shirota, Herbert T. Nagasawa

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

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Abstract

Replacement of the 5'-OH group of puromycin aminonucleoside (PAN) with H resulted in the elimination of kidney toxicity associated with administration of PAN. Thus, 5'-deoxy-PAN was not nephrotoxic to rats under the usual criteria. The corresponding 5'-deoxypuromycin derived from 5'-deoxy-PAN was examined in a ribosomal peptidyl transferase assay and was found to be an excellent substrate for the transpeptidation reaction with bacterial ribosomes; the Km was 0.29 mM compared to the Km for puromycin of 0.20 mM. Thus, a puromycin analog has been prepared which retains puromycin-like activity at the ribosomal level, but which is capable of releasing only a non-nephrotoxic aminonucleoside by enzymatic hydrolysis of the p-methoxyphenylalanyl side-chain.

Original language	English (US)
Pages (from-to)	345-349
Number of pages	5
Journal	Life Sciences
Volume	18
Issue number	3
DOIs	https://doi.org/10.1016/0024-3205(76)90063-1
State	Published - Feb 1 1976

Bibliographical note

Funding Information:
This investigation was supported by Research Career Development Award CA25258 (to R. V .) and Grant CA 13592 from the National Cancer Institute, and Training Grant 5 T01 GM 02064 from the National Institutes of Health, U.S. Public Health Service.

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title = "An active puromycin analog derived from a non-nephrotoxic aminonucleoside",

abstract = "Replacement of the 5'-OH group of puromycin aminonucleoside (PAN) with H resulted in the elimination of kidney toxicity associated with administration of PAN. Thus, 5'-deoxy-PAN was not nephrotoxic to rats under the usual criteria. The corresponding 5'-deoxypuromycin derived from 5'-deoxy-PAN was examined in a ribosomal peptidyl transferase assay and was found to be an excellent substrate for the transpeptidation reaction with bacterial ribosomes; the Km was 0.29 mM compared to the Km for puromycin of 0.20 mM. Thus, a puromycin analog has been prepared which retains puromycin-like activity at the ribosomal level, but which is capable of releasing only a non-nephrotoxic aminonucleoside by enzymatic hydrolysis of the p-methoxyphenylalanyl side-chain.",

author = "Robert Vince and Almquist, {Ronald G.} and Ritter, {Clare L.} and Shirota, {Frances N.} and Nagasawa, {Herbert T.}",

note = "Funding Information: This investigation was supported by Research Career Development Award CA25258 (to R. V .) and Grant CA 13592 from the National Cancer Institute, and Training Grant 5 T01 GM 02064 from the National Institutes of Health, U.S. Public Health Service.",

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T1 - An active puromycin analog derived from a non-nephrotoxic aminonucleoside

AU - Vince, Robert

AU - Almquist, Ronald G.

AU - Ritter, Clare L.

AU - Shirota, Frances N.

AU - Nagasawa, Herbert T.

N1 - Funding Information: This investigation was supported by Research Career Development Award CA25258 (to R. V .) and Grant CA 13592 from the National Cancer Institute, and Training Grant 5 T01 GM 02064 from the National Institutes of Health, U.S. Public Health Service.

PY - 1976/2/1

Y1 - 1976/2/1

N2 - Replacement of the 5'-OH group of puromycin aminonucleoside (PAN) with H resulted in the elimination of kidney toxicity associated with administration of PAN. Thus, 5'-deoxy-PAN was not nephrotoxic to rats under the usual criteria. The corresponding 5'-deoxypuromycin derived from 5'-deoxy-PAN was examined in a ribosomal peptidyl transferase assay and was found to be an excellent substrate for the transpeptidation reaction with bacterial ribosomes; the Km was 0.29 mM compared to the Km for puromycin of 0.20 mM. Thus, a puromycin analog has been prepared which retains puromycin-like activity at the ribosomal level, but which is capable of releasing only a non-nephrotoxic aminonucleoside by enzymatic hydrolysis of the p-methoxyphenylalanyl side-chain.

AB - Replacement of the 5'-OH group of puromycin aminonucleoside (PAN) with H resulted in the elimination of kidney toxicity associated with administration of PAN. Thus, 5'-deoxy-PAN was not nephrotoxic to rats under the usual criteria. The corresponding 5'-deoxypuromycin derived from 5'-deoxy-PAN was examined in a ribosomal peptidyl transferase assay and was found to be an excellent substrate for the transpeptidation reaction with bacterial ribosomes; the Km was 0.29 mM compared to the Km for puromycin of 0.20 mM. Thus, a puromycin analog has been prepared which retains puromycin-like activity at the ribosomal level, but which is capable of releasing only a non-nephrotoxic aminonucleoside by enzymatic hydrolysis of the p-methoxyphenylalanyl side-chain.

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DO - 10.1016/0024-3205(76)90063-1

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AN - SCOPUS:0017265205

SN - 0024-3205

VL - 18

SP - 345

EP - 349

JO - Life Sciences

JF - Life Sciences

IS - 3

ER -

An active puromycin analog derived from a non-nephrotoxic aminonucleoside

Abstract

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