1106998-86-0Relevant articles and documents
Structural analysis of ARC-type inhibitor (ARC-1034) binding to protein kinase A catalytic subunit and rational design of bisubstrate analogue inhibitors of basophilic protein kinases
Lavogina, Darja,Lust, Marje,Viil, Indrek,K?nig, Norbert,Raidaru, Gerda,Rogozina, Jevgenia,Enkvist, Erki,Uri, Asko,Bossemeyer, Dirk
supporting information; experimental part, p. 308 - 321 (2009/10/01)
The crystal structure of a complex of the catalytic subunit (type α) of cAMP-dependent protein kinase (PKA Cα) with ARC-type inhibitor (ARC-1034), the presumed lead scaffold of previously reported adenosineoligo-arginine conjugate-based (ARC-type) inhibitors, was solved. Structural elements important for interaction with the kinase were established with specifically modified derivatives of the lead compound. On the basis of this knowledge, a new generation of inhibitors, conjugates of adenosine-4′-dehydroxymethyl-4′-carboxylic acid moiety and oligo(D-arginine), was developed with inhibitory constants well into the subnanomolar range. The structural determinants of selectivity of the new compounds were established in assays with ROCK-II and PKBy.
