Przejdź do zawartości
Merck
  • Multiple and single binding modes of fragment-like kinase inhibitors revealed by molecular modeling, residue type-selective protonation, and nuclear overhauser effects.

Multiple and single binding modes of fragment-like kinase inhibitors revealed by molecular modeling, residue type-selective protonation, and nuclear overhauser effects.

Journal of medicinal chemistry (2008-09-06)
Keith L Constantine, Luciano Mueller, William J Metzler, Patricia A McDonnell, Gordon Todderud, Valentina Goldfarb, Yi Fan, John A Newitt, Susan E Kiefer, Mian Gao, David Tortolani, Wayne Vaccaro, John Tokarski
ABSTRAKT

Fragment-like inhibitors of mitogen-activated protein kinase-activated protein kinase 2 (MK2) include 5-hydroxyisoquinoline (IC50 approximately 85 microM). Modeling studies identified four possible binding modes for this compound. Two-dimensional (1)H-(1)H NOESY data obtained with selectively protonated samples of MK2 in complex with 5-hydroxyisoquinoline demonstrated that two of the four predicted binding modes are well populated. A second small isoquinoline was subsequently shown to bind in a single mode. NMR and modeling studies using this general approach are expected to facilitate "scaffold hopping" and structure-guided elaborations of fragment-like kinase inhibitor cores.

MATERIAŁY
Numer produktu
Marka
Opis produktu

Sigma-Aldrich
1-Naphthol, BioXtra, ≥99%
Sigma-Aldrich
1-Naphthol, ReagentPlus®, ≥99%
Sigma-Aldrich
1-Naphthol, puriss. p.a., reag. Ph. Eur., ≥99% (GC)
Sigma-Aldrich
5-Hydroxyisoquinoline, technical grade, 90%