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Structure-Based Design of Potent and Selective LeishmaniaN-Myristoyltransferase Inhibitors
[Image: see text] Inhibitors of LeishmaniaN-myristoyltransferase (NMT), a potential target for the treatment of leishmaniasis, obtained from a high-throughput screen, were resynthesized to validate activity. Crystal structures bound to Leishmania major NMT were obtained, and the active diastereoisom...
| Autores principales: | , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
American Chemical
Society
2014
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| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4211304/ https://www.ncbi.nlm.nih.gov/pubmed/25238611 http://dx.doi.org/10.1021/jm5011397 |
| _version_ | 1782341548931809280 |
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| author | Hutton, Jennie A. Goncalves, Victor Brannigan, James A. Paape, Daniel Wright, Megan H. Waugh, Thomas M. Roberts, Shirley M. Bell, Andrew S. Wilkinson, Anthony J. Smith, Deborah F. Leatherbarrow, Robin J. Tate, Edward W. |
| author_facet | Hutton, Jennie A. Goncalves, Victor Brannigan, James A. Paape, Daniel Wright, Megan H. Waugh, Thomas M. Roberts, Shirley M. Bell, Andrew S. Wilkinson, Anthony J. Smith, Deborah F. Leatherbarrow, Robin J. Tate, Edward W. |
| author_sort | Hutton, Jennie A. |
| collection | PubMed |
| description | [Image: see text] Inhibitors of LeishmaniaN-myristoyltransferase (NMT), a potential target for the treatment of leishmaniasis, obtained from a high-throughput screen, were resynthesized to validate activity. Crystal structures bound to Leishmania major NMT were obtained, and the active diastereoisomer of one of the inhibitors was identified. On the basis of structural insights, enzyme inhibition was increased 40-fold through hybridization of two distinct binding modes, resulting in novel, highly potent Leishmania donovani NMT inhibitors with good selectivity over the human enzyme. |
| format | Online Article Text |
| id | pubmed-4211304 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2014 |
| publisher | American Chemical
Society |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-42113042014-10-29 Structure-Based Design of Potent and Selective LeishmaniaN-Myristoyltransferase Inhibitors Hutton, Jennie A. Goncalves, Victor Brannigan, James A. Paape, Daniel Wright, Megan H. Waugh, Thomas M. Roberts, Shirley M. Bell, Andrew S. Wilkinson, Anthony J. Smith, Deborah F. Leatherbarrow, Robin J. Tate, Edward W. J Med Chem [Image: see text] Inhibitors of LeishmaniaN-myristoyltransferase (NMT), a potential target for the treatment of leishmaniasis, obtained from a high-throughput screen, were resynthesized to validate activity. Crystal structures bound to Leishmania major NMT were obtained, and the active diastereoisomer of one of the inhibitors was identified. On the basis of structural insights, enzyme inhibition was increased 40-fold through hybridization of two distinct binding modes, resulting in novel, highly potent Leishmania donovani NMT inhibitors with good selectivity over the human enzyme. American Chemical Society 2014-09-19 2014-10-23 /pmc/articles/PMC4211304/ /pubmed/25238611 http://dx.doi.org/10.1021/jm5011397 Text en Copyright © 2014 American Chemical Society Terms of Use CC-BY (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) |
| spellingShingle | Hutton, Jennie A. Goncalves, Victor Brannigan, James A. Paape, Daniel Wright, Megan H. Waugh, Thomas M. Roberts, Shirley M. Bell, Andrew S. Wilkinson, Anthony J. Smith, Deborah F. Leatherbarrow, Robin J. Tate, Edward W. Structure-Based Design of Potent and Selective LeishmaniaN-Myristoyltransferase Inhibitors |
| title | Structure-Based Design of
Potent and Selective LeishmaniaN-Myristoyltransferase
Inhibitors |
| title_full | Structure-Based Design of
Potent and Selective LeishmaniaN-Myristoyltransferase
Inhibitors |
| title_fullStr | Structure-Based Design of
Potent and Selective LeishmaniaN-Myristoyltransferase
Inhibitors |
| title_full_unstemmed | Structure-Based Design of
Potent and Selective LeishmaniaN-Myristoyltransferase
Inhibitors |
| title_short | Structure-Based Design of
Potent and Selective LeishmaniaN-Myristoyltransferase
Inhibitors |
| title_sort | structure-based design of
potent and selective leishmanian-myristoyltransferase
inhibitors |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4211304/ https://www.ncbi.nlm.nih.gov/pubmed/25238611 http://dx.doi.org/10.1021/jm5011397 |
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