Identification of small peptides mimicking the R2 C-terminus of Mycobacterium tuberculosis ribonucleotide reductase.
Ribonucleotide reductase (RNR) is a viable target for new drugs against the causative agent of tuberculosis, Mycobacterium tuberculosis. Previous work has shown that an N-acetylated heptapeptide based on the C-terminal sequence of the smaller RNR subunit can disrupt the formation of the holoenzyme sufficiently to inhibit its function. Here the synthesis and binding affinity, evaluated by competitive fluorescence polarization, of several truncated and N-protected peptides are described. The protected single-amino acid Fmoc-Trp shows binding affinity comparable to the N-acetylated heptapeptide, making it an attractive candidate for further development of non-peptidic RNR inhibitors.
Ericsson
Daniel J
DJ
Department of Cell and Molecular Biology, Structural Biology, BMC, Uppsala University, Box 596, SE-751 24 Uppsala, Sweden.
Nurbo
Johanna
J
Muthas
Daniel
D
Hertzberg
Kalle
K
Lindeberg
Gunnar
G
Karlén
Anders
A
Unge
Torsten
T
D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D009842:Oligopeptides / Q000032:analysis* / Q000138:chemical synthesis / Q000737:chemistry*; D012264:Ribonucleotide Reductases / Q000737:chemistry*
D009842:Oligopeptides; D012264:Ribonucleotide Reductases