Conjugates of 5-isoquinolinesulfonylamides and oligo-D-arginine possess high affinity and selectivity towards Rho kinase (ROCK).
Basic Information
ID: ALA2021921
Journal: Bioorg Med Chem Lett
Title: Conjugates of 5-isoquinolinesulfonylamides and oligo-D-arginine possess high affinity and selectivity towards Rho kinase (ROCK).
Authors: Lavogina D, Kalind K, Bredihhina J, Hurt M, Vaasa A, Kasari M, Enkvist E, Raidaru G, Uri A.
Abstract: In the present work, conjugates of 5-isoquinolinesulfonylamides and D-arginine-rich peptides were developed into highly potent inhibitors for basophilic protein kinases. Based on Hidaka's inhibitor H9, a generic fluorescent probe ARC-1083 was constructed possessing subnanomolar dissociation constant towards several kinases of the AGC-group. Thereafter, Hidaka's inhibitor HA1077 or Fasudil was conjugated with oligo-D-arginine resulting in the compound ARC-3002 revealing high affinity towards ROCK-II (K(d)=20 pM) and over 160-fold selectivity compared to PKAc.
CiteXplore: 22521647
DOI: 10.1016/j.bmcl.2012.03.101
Patent ID: ┄