Three-Dimensional Database Mining Identifies a Unique Chemotype that Unites Structurally Diverse Botulinum Neurotoxin Serotype A Inhibitors in a Three-Zone Pharmacophore
Nema prikaza
Autori
Hermone, Ann R.Burnett, James C.
Nuss, Jonathan E.
Tressler, Lyal E.
Nguyen, Tam L.
Šolaja, Bogdan A.
Vennerstrom, Jonathan L.
Schmidt, James J.
Wipf, Peter
Bavari, Sina
Gussio, Rick
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
A search query consisting of two aromatic centers and two cationic centers was defined based on previously identified small molecule inhibitors of the botulinum neurotoxin serotype A light chain (BoNT/A LC) and used to mine the National Cancer Institute Open Repository. Ten small molecule hits were identified, and upon testing, three demonstrated inhibitory activity. Of these, one was structurally unique, possessing a rigid diazochrysene scaffold. The steric limitations of the diazachrysene imposed a separation between the overlaps of previously identified inhibitors, revealing an extended binding mode. As a result, the pharmacophore for BoNT/A LC inhibition has been modified to encompass three zones. To demonstrate the utility of this model, a novel three-zone inhibitor was mined and its activity was confirmed.
Ključne reči:
molecular modeling / screening / drug discovery / biologically active compounds / botulinum neurotoxinIzvor:
ChemMedChem, 2008, 3, 12, 1905-1912Izdavač:
- Wiley-V C H Verlag Gmbh, Weinheim
DOI: 10.1002/cmdc.200800241
ISSN: 1860-7179
PubMed: 19006141
WoS: 000261877100011
Scopus: 2-s2.0-57549112239
Kolekcije
Institucija/grupa
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Hermone, Ann R. AU - Burnett, James C. AU - Nuss, Jonathan E. AU - Tressler, Lyal E. AU - Nguyen, Tam L. AU - Šolaja, Bogdan A. AU - Vennerstrom, Jonathan L. AU - Schmidt, James J. AU - Wipf, Peter AU - Bavari, Sina AU - Gussio, Rick PY - 2008 UR - https://cherry.chem.bg.ac.rs/handle/123456789/593 AB - A search query consisting of two aromatic centers and two cationic centers was defined based on previously identified small molecule inhibitors of the botulinum neurotoxin serotype A light chain (BoNT/A LC) and used to mine the National Cancer Institute Open Repository. Ten small molecule hits were identified, and upon testing, three demonstrated inhibitory activity. Of these, one was structurally unique, possessing a rigid diazochrysene scaffold. The steric limitations of the diazachrysene imposed a separation between the overlaps of previously identified inhibitors, revealing an extended binding mode. As a result, the pharmacophore for BoNT/A LC inhibition has been modified to encompass three zones. To demonstrate the utility of this model, a novel three-zone inhibitor was mined and its activity was confirmed. PB - Wiley-V C H Verlag Gmbh, Weinheim T2 - ChemMedChem T1 - Three-Dimensional Database Mining Identifies a Unique Chemotype that Unites Structurally Diverse Botulinum Neurotoxin Serotype A Inhibitors in a Three-Zone Pharmacophore VL - 3 IS - 12 SP - 1905 EP - 1912 DO - 10.1002/cmdc.200800241 ER -
@article{ author = "Hermone, Ann R. and Burnett, James C. and Nuss, Jonathan E. and Tressler, Lyal E. and Nguyen, Tam L. and Šolaja, Bogdan A. and Vennerstrom, Jonathan L. and Schmidt, James J. and Wipf, Peter and Bavari, Sina and Gussio, Rick", year = "2008", abstract = "A search query consisting of two aromatic centers and two cationic centers was defined based on previously identified small molecule inhibitors of the botulinum neurotoxin serotype A light chain (BoNT/A LC) and used to mine the National Cancer Institute Open Repository. Ten small molecule hits were identified, and upon testing, three demonstrated inhibitory activity. Of these, one was structurally unique, possessing a rigid diazochrysene scaffold. The steric limitations of the diazachrysene imposed a separation between the overlaps of previously identified inhibitors, revealing an extended binding mode. As a result, the pharmacophore for BoNT/A LC inhibition has been modified to encompass three zones. To demonstrate the utility of this model, a novel three-zone inhibitor was mined and its activity was confirmed.", publisher = "Wiley-V C H Verlag Gmbh, Weinheim", journal = "ChemMedChem", title = "Three-Dimensional Database Mining Identifies a Unique Chemotype that Unites Structurally Diverse Botulinum Neurotoxin Serotype A Inhibitors in a Three-Zone Pharmacophore", volume = "3", number = "12", pages = "1905-1912", doi = "10.1002/cmdc.200800241" }
Hermone, A. R., Burnett, J. C., Nuss, J. E., Tressler, L. E., Nguyen, T. L., Šolaja, B. A., Vennerstrom, J. L., Schmidt, J. J., Wipf, P., Bavari, S.,& Gussio, R.. (2008). Three-Dimensional Database Mining Identifies a Unique Chemotype that Unites Structurally Diverse Botulinum Neurotoxin Serotype A Inhibitors in a Three-Zone Pharmacophore. in ChemMedChem Wiley-V C H Verlag Gmbh, Weinheim., 3(12), 1905-1912. https://doi.org/10.1002/cmdc.200800241
Hermone AR, Burnett JC, Nuss JE, Tressler LE, Nguyen TL, Šolaja BA, Vennerstrom JL, Schmidt JJ, Wipf P, Bavari S, Gussio R. Three-Dimensional Database Mining Identifies a Unique Chemotype that Unites Structurally Diverse Botulinum Neurotoxin Serotype A Inhibitors in a Three-Zone Pharmacophore. in ChemMedChem. 2008;3(12):1905-1912. doi:10.1002/cmdc.200800241 .
Hermone, Ann R., Burnett, James C., Nuss, Jonathan E., Tressler, Lyal E., Nguyen, Tam L., Šolaja, Bogdan A., Vennerstrom, Jonathan L., Schmidt, James J., Wipf, Peter, Bavari, Sina, Gussio, Rick, "Three-Dimensional Database Mining Identifies a Unique Chemotype that Unites Structurally Diverse Botulinum Neurotoxin Serotype A Inhibitors in a Three-Zone Pharmacophore" in ChemMedChem, 3, no. 12 (2008):1905-1912, https://doi.org/10.1002/cmdc.200800241 . .