tetano
Editor, Senior Moderator
Org Biomol Chem. 2012 Sep 14. [Epub ahead of print]
Synthesis and evaluation of novel 3-C-alkylated-Neu5Ac2en derivatives as probes of influenza virus sialidase 150-loop flexibility.
Rudrawar S, Kerry PS, Rameix-Welti MA, Maggioni A, Dyason JC, Rose FJ, van der Werf S, Thomson RJ, Naffakh N, Russell RJ, von Itzstein M.
Source
Institute for Glycomics, Gold Coast Campus, Griffith University, Queensland 4222, Australia. m.vonitzstein@griffith.edu.au.
Abstract
Novel 3-C-alkylated-Neu5Ac2en derivatives have been designed to target the expanded active site cavity of influenza virus sialidases with an open 150-loop, currently seen in X-ray crystal structures of influenza A virus group-1 (N1, N4, N5, N8), but not group-2 (N2, N9), sialidases. The compounds show selectivity for inhibition of H5N1 and pdm09 H1N1 sialidases over an N2 sialidase, providing evidence of the relative 150-loop flexibility of these sialidases. In a complex with N8 sialidase, the C3 substituent of 3-phenylally-Neu5Ac2en occupies the 150-cavity while the central ring and the remaining substituents bind the active site as seen for the unsubstituted template. This new class of inhibitors, which can 'trap' the open 150-loop form of the sialidase, should prove useful as probes of 150-loop flexibility.
PMID:
22976385
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22976385
Synthesis and evaluation of novel 3-C-alkylated-Neu5Ac2en derivatives as probes of influenza virus sialidase 150-loop flexibility.
Rudrawar S, Kerry PS, Rameix-Welti MA, Maggioni A, Dyason JC, Rose FJ, van der Werf S, Thomson RJ, Naffakh N, Russell RJ, von Itzstein M.
Source
Institute for Glycomics, Gold Coast Campus, Griffith University, Queensland 4222, Australia. m.vonitzstein@griffith.edu.au.
Abstract
Novel 3-C-alkylated-Neu5Ac2en derivatives have been designed to target the expanded active site cavity of influenza virus sialidases with an open 150-loop, currently seen in X-ray crystal structures of influenza A virus group-1 (N1, N4, N5, N8), but not group-2 (N2, N9), sialidases. The compounds show selectivity for inhibition of H5N1 and pdm09 H1N1 sialidases over an N2 sialidase, providing evidence of the relative 150-loop flexibility of these sialidases. In a complex with N8 sialidase, the C3 substituent of 3-phenylally-Neu5Ac2en occupies the 150-cavity while the central ring and the remaining substituents bind the active site as seen for the unsubstituted template. This new class of inhibitors, which can 'trap' the open 150-loop form of the sialidase, should prove useful as probes of 150-loop flexibility.
PMID:
22976385
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22976385