Conjugates of 5-isoquinolinesulfonylamides and oligo-d-arginine possess high affinity and selectivity towards Rho kinase (ROCK)

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 (Kd = 20 pM) and over 160-fold selectivity compared to PKAc.

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