Effect on protein phosphatase activity of peptide backbone modification and truncation of the autoinhibitory domain peptide of calcineurin.
Solid-phase synthesis of the autoinhibitory domain of calcineurin, CaN A467-491, also produced [aspartimide477]CaN A467-491 and [iso-Asp477]CaN467-491 when Boc-based chemistry was employed. In addition, the truncated peptide CaN A467-488 was obtained when Fmoc-based chemistry was employed. All four peptides proved to be effective inhibitors of protein phosphatase activity of calcineurin. The full-length peptide and the C-terminally truncated peptide (CaN467-488) were indistinguishable, with Ki values of 28 +/- 3 and 31 +/- 5 mu M, respectively. The internally modified peptides, [iso-Asp477]CaN A467-491 and [aspartimide477]-CaN A467-491, possessed lower inhibitory potencies (Ki values of 87 +/- 10 and 55 +/- 3 mu M, respectively).
Bannow
C A
CA
Upjohn Laboratories, Kalamazoo, Michigan, USA.
Staples
D J
DJ
Smith
C W
CW
Chapman
D L
DL
Leach
K L
KL
D000595:Amino Acid Sequence; D019703:Calcineurin; D002148:Calmodulin-Binding Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D017434:Protein Structure, Tertiary
D002148:Calmodulin-Binding Proteins; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases