Synthesis and disulfide bond connectivity-activity studies of a kalata B1-inspired cyclopeptide against dengue NS2B-NS3 protease

被引：45

作者：

Gao, Yaojun ^{[2
]}

Cui, Taian ^{[1
]}

Lam, Yulin ^{[2
]}

机构：

[1] Singapore Polytech, Sch Chem & Life Sci, Singapore 139651, Singapore

[2] Natl Univ Singapore, Dept Chem, Singapore 117543, Singapore

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2010年 / 18卷 / 03期

关键词：

Dengue NS2B-NS3 protease; VIRUS NS3 PROTEASE; PEPTIDE INHIBITORS; SERINE-PROTEASE; CLEAVAGE; PROTEINS; IDENTIFICATION; CYCLOTIDES; EFFICIENT; COFACTOR; TYPE-2;

D O I：

10.1016/j.bmc.2009.12.026

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Kalata B1 is a plant protein with remarkable thermal, chemical and enzymatic stability. Its potential applications could be centered on the possibility of using its cyclic structure and cystine knot motif as a scaffold for the design of stable pharmaceuticals. To discover potent dengue NS2B-NS3 protease inhibitors, we have prepared various kalata B1 analogues by varying the amino acid sequence. Mass spectrometric and biochemical investigations of these analogues revealed a cyclopeptide whose two fully oxidized forms are substrate-competitive inhibitors of the dengue viral NS2B-NS3 protease. Both oxidized forms showed potent inhibition with Ki of 1.39 +/- 0.35 and 3.03 +/- 0.75 mu M, respectively. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：1331 / 1336

页数：6

共 30 条

[1]

Competitive inhibition of the dengue virus NS3 serine protease by synthetic peptides representing polyprotein cleavage sites [J].

Chanprapaph, S ;

Saparpakorn, P ;

Sangma, C ;

Niyomrattanakit, P ;

Hannongbua, S ;

Angsuthanasombat, C ;

Katzenmeier, G .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2005, 330 (04) :1237-1246

[2]

West Nile Virus NS2B/NS3 Protease As An Antiviral Target [J].

Chappell, K. J. ;

Stoermer, M. J. ;

Fairlie, D. P. ;

Young, P. R. .

CURRENT MEDICINAL CHEMISTRY, 2008, 15 (27) :2771-2784

[3]

Cotranslational membrane insertion of the serine proteinase precursor NS2B-NS3(Pro) of dengue virus type 2 is required for efficient in vitro processing and is mediated through the hydrophobic regions of NS2B [J].

Clum, S ;

Ebner, KE ;

Padmanabhan, R .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (49) :30715-30723

[4]

Plant cyclotides: A unique family of cyclic and knotted proteins that defines the cyclic cystine knot structural motif [J].

Craik, DJ ;

Daly, NL ;

Bond, T ;

Waine, C .

JOURNAL OF MOLECULAR BIOLOGY, 1999, 294 (05) :1327-1336

[5]

Craik DJ, 2002, CURR OPIN DRUG DI DE, V5, P251

[6]

CUI T, 2007, Patent No. 2007149052

[7]

BOTH NONSTRUCTURAL PROTEINS NS2B AND NS3 ARE REQUIRED FOR THE PROTEOLYTIC PROCESSING OF DENGUE VIRUS NONSTRUCTURAL PROTEINS [J].

FALGOUT, B ;

PETHEL, M ;

ZHANG, YM ;

LAI, CJ .

JOURNAL OF VIROLOGY, 1991, 65 (05) :2467-2475

[8]

Identification and characterization of nonsubstrate based inhibitors of the essential Dengue and West Nile virus proteases [J].

Ganesh, VK ;

Muller, N ;

Judge, K ;

Luan, CH ;

Padmanabhan, R ;

Murthy, KHM .

BIOORGANIC & MEDICINAL CHEMISTRY, 2005, 13 (01) :257-264

[9]

Disulfide mapping of the cyclotide kalata B1 -: Chemical proof of the cyclic cystine knot motif [J].

Göransson, U ;

Craik, DJ .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (48) :48188-48196

[10]

Squash trypsin inhibitors from Momordica cochinchinensis exhibit an atypical macrocyclic structure [J].

Hernandez, JF ;

Gagnon, J ;

Chiche, L ;

Nguyen, TM ;

Andrieu, JP ;

Heitz, A ;

Hong, TT ;

Pham, TTC ;

Nguyen, DL .

BIOCHEMISTRY, 2000, 39 (19) :5722-5730

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