Inhibition of protein kinase C by retro-inverso pseudosubstrate analogues.
A retro-inverso analogue of the pseudosubstrate sequence, Arg-Phe-Ala-Arg-Lys-Gly-Ala25-Leu-Arg-Gln-Lys-Asn-Val (1), found in the regulatory domain of all protein kinase C (PKC) subspecies was synthesized. It shows to be an inhibitor (IC50 = 31 microM) of the phosphorylation, by PKC, of [Ala9.10,Lys11.12] glycogen synthase (1-12). Its analogue in which D Ala25 is replaced by D Ser is not a PKC substrate, but a more potent inhibitor, competitive with the peptidic substrate (IC50 = 5 microM, Ki = 2 microM). Both retro-inverso peptides are highly specific for PKC versus adenosine cAMP-dependent protein kinase (PKA) and are totally stable towards proteolysis by trypsin or pronase.
Ricouart
A
A
Institut Pasteur de Lille, Service de Chimie des Biomolécules, France.
Tartar
A
A
Sergheraert
C
C
D000595:Amino Acid Sequence; D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D006006:Glycogen Synthase / Q000378:metabolism; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism; D010766:Phosphorylation; D011402:Pronase / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014357:Trypsin / Q000378:metabolism
D009842:Oligopeptides; D010446:Peptide Fragments; D006006:Glycogen Synthase; D011493:Protein Kinase C; D014357:Trypsin; D011402:Pronase