Design, synthesis and evaluation of peptide inhibitors of Mycobacterium tuberculosis ribonucleotide reductase
2007 (English)In: Journal of Peptide Science, ISSN 1075-2617, Vol. 13, no 12, 822-832 p.Article in journal (Refereed) Published
Mycobacterium tuberculosis ribonucleotide reductase (RNR) is a potential target for new antitubercular drugs. Herein we describe the synthesis and evaluation of peptide inhibitors of RNR derived from the C-terminus of the small subunit of M. tuberculosis RNR. An N-terminal truncation, an alanine scan and a novel statistical molecular design (SMD) approach based on the heptapeptide Ac-Glu-Asp-Asp-Asp-Trp-Asp-Phe-OH were applied in this study. The alanine scan showed that TrP5 and Phe7 were important for inhibitory potency. A quantitative structure relationship (QSAR) model was developed based on the synthesized peptides which showed that a negative charge in positions 2, 3, and 6 is beneficial for inhibitory potency. Finally, in position 5 the model coefficients indicate that there is room for a larger side chain., as compared to Trp5.
Place, publisher, year, edition, pages
2007. Vol. 13, no 12, 822-832 p.
mycobacterium tuberculosis, ribonucleotide reductase, peptide inhibitors, alanine scan, statistical molecular design, structure activity relationships, FHDoE
IdentifiersURN: urn:nbn:se:uu:diva-14261DOI: 10.1002/psc.906ISI: 000252000600007PubMedID: 17918768OAI: oai:DiVA.org:uu-14261DiVA: diva2:42031