title: Conjugates of 5-isoquinolinesulfonylamides and oligo-D-arginine possess high affinity and selectivity towards Rho kinase (ROCK).
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.
authors.affiliation: Institute of Chemistry, University of Tartu, Tartu, Estonia.
authors.forename: Darja
authors.initials: D
authors.lastname: Lavogina
authors.forename: Katrin
authors.initials: K
authors.lastname: Kalind
authors.forename: Jevgenia
authors.initials: J
authors.lastname: Bredihhina
authors.forename: Madis
authors.initials: M
authors.lastname: Hurt
authors.forename: Angela
authors.initials: A
authors.lastname: Vaasa
authors.forename: Marje
authors.initials: M
authors.lastname: Kasari
authors.forename: Erki
authors.initials: E
authors.lastname: Enkvist
authors.forename: Gerda
authors.initials: G
authors.lastname: Raidaru
authors.forename: Asko
authors.initials: A
authors.lastname: Uri
mesh_terms: D001120:Arginine / Q000737:chemistry* / Q000494:pharmacology; D007546:Isoquinolines / Q000737:chemistry* / Q000494:pharmacology; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000187:drug effects*
chemical_list: D007546:Isoquinolines; D013449:Sulfonamides; D001120:Arginine; D054460:rho-Associated Kinases