Design, synthesis and evaluation of peptide inhibitors of Mycobacterium tuberculosis ribonucleotide reductase

Nurbo, Johanna, Roos, Annette K., Muthas, Daniel, Wahlstrom, Erik, Ericsson, Daniel J., Lundstedt, Torbjorn, Unge, Torsten and Karlen, Anders (2007) Design, synthesis and evaluation of peptide inhibitors of Mycobacterium tuberculosis ribonucleotide reductase. Journal of Peptide Science, 13 12: 822-832. doi:10.1002/psc.906


Author Nurbo, Johanna
Roos, Annette K.
Muthas, Daniel
Wahlstrom, Erik
Ericsson, Daniel J.
Lundstedt, Torbjorn
Unge, Torsten
Karlen, Anders
Title Design, synthesis and evaluation of peptide inhibitors of Mycobacterium tuberculosis ribonucleotide reductase
Formatted title
Design, synthesis and evaluation of peptide inhibitors of Mycobacterium tuberculosis ribonucleotide reductase
Journal name Journal of Peptide Science   Check publisher's open access policy
ISSN 1075-2617
1099-1387
Publication date 2007-12
Sub-type Article (original research)
DOI 10.1002/psc.906
Volume 13
Issue 12
Start page 822
End page 832
Total pages 11
Place of publication West Sussex, United Kingdom
Publisher John Wiley & Sons
Language eng
Formatted abstract
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.
Keyword mycobacterium tuberculosis
ribonucleotide reductase
peptide inhibitors
alanine scan
statistical molecular design
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: ERA 2012 Admin Only
School of Chemistry and Molecular Biosciences
 
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