Optically active cantharidin analogues possessing selective inhibitory activity on Ser/Thr protein phosphatase 2B (calcineurin): Implications for the binding mode

被引：40

作者：

Baba, Y

Hirukawa, N

Sodeoka, M

机构：

[1] Tohoku Univ, Inst Multidisciplinary Res Adv Mat, Sendai, Miyagi 9808577, Japan

[2] RIKEN, Inst Phys & Chem Res, Wako, Saitama 3510198, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2005年 / 13卷 / 17期

基金：

日本学术振兴会;

关键词：

PP2B; calcineurin; cantharidin; inhibitor; optically active;

D O I：

10.1016/j.bmc.2005.05.013

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cantharidin is well known as a potent serine/threonine protein phosphatase 1 and 2A (PP1 and PP2A) inhibitor, with less potent inhibitory activity for PP2B, which regulates T-cell proliferation. We synthesized and evaluated four optically pure stereoisomers of 1-substituted norcantharidin analogues. The absolute stereochemistry of each stereoisomer was determined based on X-ray crystal structure analysis. Remarkably, optically active cantharidin analogues having (1S)-configuration showed selective inhibition of PP2B, without inhibiting PP1 or PP2A. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：5164 / 5170

页数：7

共 27 条

[1] Structure-based design of a highly selective catalytic site-directed inhibitor of Ser/Thr protein phosphatase 2B (calcineurin)
Baba, Y
Hirukawa, N
Tanohira, N
Sodeoka, M
[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2003, 125 (32) : 9740 - 9749
[2] Reversible inhibition of calcineurin by the polyphenolic aldehyde gossypol
Baumgrass, R
Weiwad, M
Erdmann, F
Liu, JO
Wunderlich, D
Grabley, S
Fischer, G
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (51) : 47914 - 47921
[3] 7-oxa[2.2.1]bicycloheptane-2,3-dicarboxylic acid derivatives as phosphatase inhibitors
Enz, A
Zenke, G
PomboVillar, E
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1997, 7 (19) : 2513 - 2518
[4] A molecular modeling analysis of the binding interactions between the okadaic acid class of natural product inhibitors and the Ser-Thr phosphatases, PP1 and PP2A
Gauss, CM
Sheppeck, JE
Nairn, AC
Chamberlin, R
[J]. BIOORGANIC & MEDICINAL CHEMISTRY, 1997, 5 (09) : 1751 - 1773
[5] 3-DIMENSIONAL STRUCTURE OF THE CATALYTIC SUBUNIT OF PROTEIN SERINE/THREONINE PHOSPHATASE-1
GOLDBERG, J
HUANG, HB
KWON, YG
GREENGARD, P
NAIRN, AC
KURIYAN, J
[J]. NATURE, 1995, 376 (6543) : 745 - 753
[6] X-RAY STRUCTURE OF CALCINEURIN INHIBITED BY THE IMMUNOPHILIN IMMUNOSUPPRESSANT FKBP12-FK506 COMPLEX
GRIFFITH, JP
KIM, JL
KIM, EE
SINTCHAK, MD
THOMSON, JA
FITZGIBBON, MJ
FLEMING, MA
CARON, PR
HSIAO, K
NAVIA, MA
[J]. CELL, 1995, 82 (03) : 507 - 522
[7] Modified norcantharidins: synthesis, protein phosphatases 1 and 2A inhibition, and anticancer activity
Hart, ME
Chamberlin, AR
Walkom, C
Sakoff, JA
McCluskey, A
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (08) : 1969 - 1973
[8] CRYSTAL-STRUCTURES OF HUMAN CALCINEURIN AND THE HUMAN FKBP12-FK506-CALCINEURIN COMPLEX
KISSINGER, CR
PARGE, HE
KNIGHTON, DR
LEWIS, CT
PELLETIER, LA
TEMPCZYK, A
KALISH, VJ
TUCKER, KD
SHOWALTER, RE
MOOMAW, EW
GASTINEL, LN
HABUKA, N
CHEN, XH
MALDONADO, F
BARKER, JE
BACQUET, R
VILLAFRANCA, JE
[J]. NATURE, 1995, 378 (6557) : 641 - 644
[9] CALCINEURIN IS A COMMON TARGET OF CYCLOPHILIN-CYCLOSPORINE-A AND FKBP-FK506 COMPLEXES
LIU, J
FARMER, JD
LANE, WS
FRIEDMAN, J
WEISSMAN, I
SCHREIBER, SL
[J]. CELL, 1991, 66 (04) : 807 - 815
[10] Inhibition of protein phosphatase 2A by cantharidin analogues.
McCluskey, A
Taylor, C
Quinn, RJ
Suganuma, M
Fujiki, H
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1996, 6 (09) : 1025 - 1028

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