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 A(467-591), also produced [aspartimide(477)]CaN A(467-491) and [iso-A sp(477)]CaN467-491 when Boc-based chemistry was employed. In addition, the truncated peptide CaN A(467-488) was Obtained when Fmoc-based che mistry was employed. All four peptides proved to be effective inhibito rs of protein phosphatase activity of calcineurin. The full-length pep tide and the C-terminally truncated peptide (CaN467-491) were indistin guishable, with K-i values of 28 +/- 3 and 31 +/- 5 mu M, respectively . The internally modified peptides, [iso-Asp(477)]CaN A(467-491) and [ aspartimide(477)]CaN A(467-491), possessed lower inhibitory potencies (K-i values of 87 +/- 10 and 55 +/- 3 mu M, respectively). (C) Munksga ard 1996.