肽主链修饰和钙调神经磷酸酶自身抑制域肽截短对蛋白磷酸酶活性的影响

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

作者信息

Bannow C A, Staples D J, Smith C W, Chapman D L, Leach K L

机构信息

Upjohn Laboratories, Kalamazoo, Michigan, USA.

出版信息

Int J Pept Protein Res. 1996 Jan-Feb;47(1-2):98-102. doi: 10.1111/j.1399-3011.1996.tb00815.x.

DOI:10.1111/j.1399-3011.1996.tb00815.x

PMID:8907505

Abstract

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).

摘要

当采用基于Boc的化学方法时，钙调神经磷酸酶自身抑制结构域CaN A467 - 491的固相合成也产生了[天冬酰胺477]CaN A467 - 491和[异天冬氨酸477]CaN467 - 491。此外，当采用基于Fmoc的化学方法时，获得了截短肽CaN A467 - 488。所有这四种肽都被证明是钙调神经磷酸酶蛋白磷酸酶活性的有效抑制剂。全长肽和C末端截短肽（CaN467 - 488）难以区分，其Ki值分别为28±3和31±5 μM。内部修饰的肽[异天冬氨酸477]CaN A467 - 491和[天冬酰胺477] - CaN A467 - 491具有较低的抑制效力（Ki值分别为87±10和55±3 μM）。