Inhibition of cGMP‐dependent protein kinase by (Rp)‐guanosine 3',5'‐monophosphorothioates

FEBS Letters

Butt, Elke²  Fischer, Lilo¹  Van Bemmelen, Michael²  Jastorff, Bernd²  Walter, Ulrich¹ 

[1] Labor für Klinische Biochemie, Medizinische Universitätsklinik, Josef-Schneider-Str. 2, D-8700 Würzburg, FRG;Universität Bremen, Fachbereich Chemie, Leobener Str., D-2800 Bremen 33 FRG

关键词: Protein kinase;    cGMP-dependent;    Antagonist;    cGMPS;    8-Cl-cGMPS;    cAK;    cAMP-dependent protein kinase;    cGK;    cGMP-dependent protein kinase;    8-Cl-cGMP;    8-chloro-8-cGMP;    (Rp)- and (Sp)-cGMPS;    phosphorothioate stereoisomers of cGMP;    (Rp)- and (Sp)-8-Cl-cGMPS;    phosphorothioate stereoisomers of 8-chloro-cGMP;    (Rp)- and (Sp)-cAMPS;    phosphorothioate stereoisomers of cAMP;    cPDE;    calmodulin-sensitive cyclic nucleotide phosphodiesterase;   

DOI  :  10.1016/0014-5793(90)80702-K

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The activation of the cGMP-dependent protein kinase and cAMP-dependent protein kinase by the diastereomers of guanosine 3',5'-monophosphorothioate, (Sp)-cGMPS and (Rp)-cGMPS, and 8-chloroguanosine 3',5'-monophosphorothioate, (Sp)-8-Cl-cGMPS and (Rp)-8-Cl-cGMPS, was investigated using the peptide Kemptide as substrate. The (Sp)-diastereomers, which have an axial exocyclic sulfur atom, bound to the cGMP-dependent protein kinase and stimulated its phosphotransferase activity. In contrast, the (Rp)-isomers, which have an equatorial exocyclic sulfur atom, bound to the enzyme without stimulation of its activity. (Rp)-cGMPS and (Rp)-8-Cl-cGMPS antagonized the activation of the cGMP-dependent protein kinase with a K _i of 20 μM and 1.5 μM, respectively. (Rp)-cGMPS also antagonized the activation of cAMP-dependent protein kinase with a K _i of 20 μM. In contrast, (Rp)-8-Cl-cGMPS was a weak inhibitor of the cAMP-dependent protein kinase with a K _i of 100 μM. (Rp)-8-Cl-cGMPS appears to be a rather selective inhibitor of the cGMP-dependent protein kinase and may be a useful tool for studying the role of cGMP in broken and intact cell systems.

【 授权许可】

Unknown