Show simple item record

dc.contributor.authorTanpure, Rajendra P
dc.contributor.authorRen, Bin
dc.contributor.authorPeat, Thomas S
dc.contributor.authorBornaghi, Laurent F
dc.contributor.authorVullo, Daniela
dc.contributor.authorSupuran, Claudiu T
dc.contributor.authorPoulsen, Sally-Ann
dc.date.accessioned2017-11-28T01:31:48Z
dc.date.available2017-11-28T01:31:48Z
dc.date.issued2015
dc.identifier.issn0022-2623
dc.identifier.doi10.1021/jm501798g
dc.identifier.urihttp://hdl.handle.net/10072/101274
dc.description.abstractWe present a new approach to carbonic anhydrase II (CA II) inhibitor design that enables close interrogation of the regions of the CA active site where there is the greatest variability in amino acid residues among the different CA isozymes. By appending dual tail groups onto the par excellence CA inhibitor acetazolamide, compounds that may interact with the distinct hydrophobic and hydrophilic halves of the CA II active site were prepared. The dual-tail combinations selected included (i) two hydrophobic moieties, (ii) two hydrophilic moieties, and (iii) one hydrophobic and one hydrophilic moiety. The CA enzyme inhibition profile as well as the protein X-ray crystal structure of compound 3, comprising one hydrophobic and one hydrophilic tail moiety, in complex with CA II is described. This novel dual-tail approach has provided an enhanced opportunity to more fully exploit interactions with the CA active site by enabling these molecules to interact with the distinct halves of the active site. In addition to the dual-tail compounds, a corresponding set of single-tail derivatives was synthesized, enabling a comparative analysis of the single-tail versus dual-tail compound CA inhibition profile.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Chemical Society
dc.relation.ispartofpagefrom1494
dc.relation.ispartofpageto1501
dc.relation.ispartofissue3
dc.relation.ispartofjournalJournal of Medicinal Chemistry
dc.relation.ispartofvolume58
dc.subject.fieldofresearchMedicinal and biomolecular chemistry
dc.subject.fieldofresearchMedicinal and biomolecular chemistry not elsewhere classified
dc.subject.fieldofresearchOrganic chemistry
dc.subject.fieldofresearchPharmacology and pharmaceutical sciences
dc.subject.fieldofresearchcode3404
dc.subject.fieldofresearchcode340499
dc.subject.fieldofresearchcode3405
dc.subject.fieldofresearchcode3214
dc.titleCarbonic anhydrase inhibitors with dual-tail moieties to match the hydrophobic and hydrophilic halves of the carbonic anhydrase active site
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.facultyGriffith Sciences, Griffith Institute for Drug Discovery
gro.hasfulltextNo Full Text
gro.griffith.authorPoulsen, Sally-Ann


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record