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Mechanisms of action of peptide inhibitors of mammalian ribonucleotide reductase targeting quaternary structure
Author(s) -
Gao Ying,
Kashlan Ossama B.,
Kaur Jaskiran,
Tan Chiheng,
Cooperman Barry S.
Publication year - 2004
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.20184
Subject(s) - ribonucleotide reductase , chemistry , peptide , ribonucleotide , biochemistry , protein quaternary structure , quaternary , action (physics) , stereochemistry , combinatorial chemistry , nucleotide , biology , protein subunit , gene , paleontology , physics , quantum mechanics
Mammalian ribonucleotide reductase (mRR) is a chemotherapeutic target. The enzyme is composed of 2 subunits (mR1 and mR2) and is inhibited by Ac‐FTLDADF (denoted P7), corresponding to the C‐terminus of mR2, which competes with mR2 for binding to mR1. mRR has 2 physiologically important active forms, mR1 2 mR2 2 and mR1 6 (mR2 2 ) j ( j = 1–3). Here we report on the mechanism of action of recently identified peptide derivatives having higher activities than P7 toward inhibition of one or both active forms. A significant feature of both P7 and these new inhibitors is that they are more potent vs. mR1 2 mR2 2 than mR1 6 (mR2 2 ) j . For some of these peptides, this is due in part to their preferential binding to the mR1 monomer. The possible application of these peptide derivatives in cancer chemotherapy is discussed. © 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2005