Towards Dynamic Drug Design: Identification and Optimization of β-Galactosidase Inhibitors from a Dynamic Hemithioacetal System
2010 (English)In: ChemBioChem (Print), ISSN 1439-4227, E-ISSN 1439-7633, Vol. 11, no 11, 1600-1606 p.Article in journal (Refereed) Published
A discovery strategy relying on the identification of fragments through resolution of a constitutional dynamic system, coupled to subsequent static ligand design and optimization, is demonstrated. The strategic design and synthesis of the best molecular fragments identified from a dynamic hemithioacetal system into static ligand structures yielded a range of -galactosidase inhibitors. Two series of structures mimicking the hemithioacetal motif were envisaged: thioglycosides and C-glycosides. Inhibition studies provided important structural information for the two groups, and 1-thiobenzyl--D-galactopyranoside demonstrated the best inhibitory effects.
Place, publisher, year, edition, pages
2010. Vol. 11, no 11, 1600-1606 p.
beta-galactosidase • dynamic chemistry • fragment-based drug discovery • inhibitors • ligand design
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
IdentifiersURN: urn:nbn:se:kth:diva-13510DOI: 10.1002/cbic.201000158ISI: 000281383200019ScopusID: 2-s2.0-77955157787OAI: oai:DiVA.org:kth-13510DiVA: diva2:325952
FunderSwedish Research Council
QC 201006212010-06-212010-06-212011-11-06Bibliographically approved