Effect on protein phosphatase activity of peptide backbone modification and truncation of the autoinhibitory domain peptide of calcineurin

• Published in: International journal of peptide and protein research Vol. 47; no. 1-2; p. 98
• Main Authors: Bannow, C A, Staples, D J, Smith, C W, Chapman, D L, Leach, K L
• Format: Journal Article
• Language: English
• Published: Denmark 01-01-1996
• Subjects: Amino Acid Sequence; Calcineurin; Calmodulin-Binding Proteins - antagonists & inhibitors; Calmodulin-Binding Proteins - chemistry; Enzyme Inhibitors - chemistry; Molecular Sequence Data; Peptide Fragments - chemistry; Phosphoprotein Phosphatases - antagonists & inhibitors; Phosphoprotein Phosphatases - chemistry; Protein Structure, Tertiary
• ISSN: 0367-8377
• DOI: 10.1111/j.1399-3011.1996.tb00815.x

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).