Paul J. Smith

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Name: Smith, Paul

Organization: University of Maryland , USA

Department: Department of Chemistry and Biochemistry

Title: Associate(PhD)

TOPICS

Organic Chemistry

Chemicals
References

Exploring the importance of zinc binding and steric/hydrophobic factors in novel HCV replication inhibitors

Co-reporter:Daniel C. Talley, Leen Delang, Johan Neyts, Pieter Leyssen, Paul J. Smith

Bioorganic & Medicinal Chemistry Letters 2016 Volume 26(Issue 4) pp:1196-1199

Publication Date(Web):15 February 2016

DOI:10.1016/j.bmcl.2016.01.035

Several novel compounds have been identified that inhibit the replication of hepatitis C virus in a replicon assay with EC50 values as low as 0.6 μM. Lead compounds were modified to investigate the possible role that zinc binding may play in inhibitor efficacy. In addition, the structure–activity relationship was explored to increase inhibitor efficacy and possibly identify favorable interactions within the currently unknown inhibitor binding pocket. The rationale for inhibitor design and biological results are presented herein.Download high-res image (125KB)Download full-size image

UK-1 and structural analogs are potent inhibitors of hepatitis C virus replication

Co-reporter:Dawn N. Ward, Daniel C. Talley, Mrinalini Tavag, Samrawit Menji, Paul Schaughency, Andrea Baier, Paul J. Smith

Bioorganic & Medicinal Chemistry Letters 2014 Volume 24(Issue 2) pp:609-612

Publication Date(Web):15 January 2014

DOI:10.1016/j.bmcl.2013.12.012

The bacterial natural product UK-1 and several structural analogs inhibit replication of the hepatitis C virus in the replicon assay, with IC50 values as low as 0.50 μM. The NS3 helicase has been identified as a possible target of inhibition for several of these compounds, while the remaining inhibitors act via an undetermined mechanism. Gel shift assays suggest that helicase inhibition is a direct result of inhibitor–enzyme binding as opposed to direct RNA binding, and the ATPase activity of NS3 is not affected. The syntheses and biological results are presented herein.

‘Induced-fit’ binding of an aryl phosphate by a macrobicyclic dicationic cyclodextrin derivative

Co-reporter:Steven L. Hauser

Journal of Physical Organic Chemistry 2005 Volume 18(Issue 5) pp:473-476

Publication Date(Web):20 DEC 2004

DOI:10.1002/poc.884

Binding of an aryl phosphate ester with a dicationic cyclodextrin derivative was compared to that with an analogous, more conformationally restricted cyclodextrin. Binding of the latter host occurs with an unexpected increase in binding free energy, resulting from an increase in binding enthalpy. A structural basis for this difference involving ‘induced-fit’ binding is proposed based on NMR experiments with the free host and the complex. Copyright © 2004 John Wiley & Sons, Ltd.