Submonomer synthesis of azapeptide ligands of the Insulin Receptor Tyrosine Kinase domain.
Basic Information
ID: ALA3352286
Journal: Bioorg Med Chem Lett
Title: Submonomer synthesis of azapeptide ligands of the Insulin Receptor Tyrosine Kinase domain.
Authors: Kurian LA, Silva TA, Sabatino D.
Abstract: Azapeptide ligands of the Insulin Receptor Tyrosine Kinase (IRTK) were developed by solid-phase submonomer azapeptide synthesis in sufficient isolated yields (36-55%) and purities >95% for structure-activity relationship studies. The azapeptides adopted folded geometries with some proportion of random coil according to CD and NMR spectroscopy. In vitro phosphorylation of the IRTK domain in the presence of azapeptides produced a lead inhibitor, Ac-DIazaYET-NH2 (∼50% at 400 μM) whereas the [aza-DOPA(3)] and [aza-Glu(4)] analogs were found to stimulate IRTK phosphorylations. Thus, azapeptide ligands of the IRTK provide important modulatory activity of this important class of enzymes for anti-cancer and related applications in drug discovery.
CiteXplore: 25127870
DOI: 10.1016/j.bmcl.2014.07.046
Patent ID: ┄