title: The carboxyl terminus heptapeptide of the R2 subunit of mammalian ribonucleotide reductase inhibits enzyme activity and can be used to purify the R1 subunit.
abstract: The heptapeptide, FTLDADF, identical in sequence to the last seven amino acid residues of the carboxyl terminus of the R2 subunit of mouse ribonucleotide reductase (RR), and its N alpha-acetyl derivative both inhibit calf thymus RR. The N alpha-acetyl derivative is considerably more potent, displaying a K1 of 20 microM. The same K1 was found for N-AcFTLDADF inhibition of a reconstituted ribonucleotide reductase from calf thymus R1 and mouse R2, indicating that the C-termini of calf R2 and mouse R2 might be identical. Our results, taken together with previous results of others on inhibition of viral RR, suggest that inhibition of RRs by peptides mimicking the C-terminus of R2 may be a general phenomenon. In addition, we have shown that an affinity column, FTLDADF-Sepharose 4B, can be used to prepare approximately 95% pure calf thymus R1, devoid of contamination with R2, in a very simple procedure that should be generally applicable to R1 purification from many sources.
authors.affiliation: Department of Chemistry, University of Pennsylvania, Philadelphia 19104.
authors.forename: F D
authors.initials: FD
authors.lastname: Yang
authors.forename: R A
authors.initials: RA
authors.lastname: Spanevello
authors.forename: I
authors.initials: I
authors.lastname: Celiker
authors.forename: R
authors.initials: R
authors.lastname: Hirschmann
authors.forename: H
authors.initials: H
authors.lastname: Rubin
authors.forename: B S
authors.initials: BS
authors.lastname: Cooperman
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002417:Cattle; D002846:Chromatography, Affinity; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009842:Oligopeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D013950:Thymus Gland / Q000201:enzymology
chemical_list: D009842:Oligopeptides; D010446:Peptide Fragments; D012264:Ribonucleotide Reductases