Design, modelling, synthesis and biological evaluation of peptidomimetic phosphinates as inhibitors of matrix metalloproteinases MMP-2 and MMP-8

被引：29

作者：

Bianchini, G

Aschi, M

Cavicchio, G

Crucianelli, M

Preziuso, S

Gallina, C

Nastari, A

Gavuzzo, E

Mazza, F

机构：

[1] Univ Aquila, Dipartimento Chim Ingn Chim & Mat, I-67100 Laquila, Italy

[2] Univ G DAnnunzio, Dipartimento Sci Farm, I-66013 Chieti, Italy

[3] Polifarma Res Ctr, I-00185 Rome, Italy

[4] Ist Chim Biomol, I-00184 Rome, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2005年 / 13卷 / 15期

关键词：

matrix metalloprotemases inhibitors; phosphinic acids; peptidomimetics; molecular dynamics and modelling;

D O I：

10.1016/j.bmc.2005.04.079

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

Three novel peptidomimetic phosphinate inhibitors have been synthesized and evaluated as inhibitors of matrix metalloprotemases MMP-2 and MMP-8. Their IC50 values are in the micromolar range, and one of them showed to be the most effective inhibitor of MMP-2. The differences in binding affinities for MMP-2 and MMP-8 of the three phosphinates have been rationalized by means of modelling studies and molecular dynamics simulations. (c) 2005 Elsevier Ltd. All rights reserved.

引用

收藏

页码：4740 / 4749

页数：10

相关论文

共 57 条

[1]

ESSENTIAL DYNAMICS OF PROTEINS [J].

AMADEI, A ;

LINSSEN, ABM ;

BERENDSEN, HJC .

PROTEINS-STRUCTURE FUNCTION AND GENETICS, 1993, 17 (04) :412-425

[2]

Molecular dynamics simulations with constrained roto-translational motions: Theoretical basis and statistical mechanical consistency [J].

Amadei, A ;

Chillemi, G ;

Ceruso, MA ;

Grottesi, A ;

Di Nola, A .

JOURNAL OF CHEMICAL PHYSICS, 2000, 112 (01) :9-23

[3]

Computational study of the catalytic domain of human neutrophil collagenase.: Specific role of the S3 and S′3 subsites in the interaction with a phosphonate inhibitor [J].

Aschi, M ;

Roccatano, D ;

Di Nola, A ;

Gallina, C ;

Gavuzzo, E ;

Pochetti, G ;

Pieper, M ;

Tschesche, H ;

Mazza, F .

JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 2002, 16 (03) :213-225

[4]

Molecular recognition of protein-ligand complexes: Applications to drug design [J].

Babine, RE ;

Bender, SL .

CHEMICAL REVIEWS, 1997, 97 (05) :1359-1472

[5]

MATRIX METALLOPROTEINASES - A REVIEW [J].

BIRKEDALHANSEN, H ;

MOORE, WGI ;

BODDEN, MK ;

WINDSOR, LJ ;

BIRKEDALHANSEN, B ;

DECARLO, A ;

ENGLER, JA .

CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE, 1993, 4 (02) :197-250

[6]

THE X-RAY CRYSTAL-STRUCTURE OF THE CATALYTIC DOMAIN OF HUMAN NEUTROPHIL COLLAGENASE INHIBITED BY A SUBSTRATE-ANALOG REVEALS THE ESSENTIALS FOR CATALYSIS AND SPECIFICITY [J].

BODE, W ;

REINEMER, P ;

HUBER, R ;

KLEINE, T ;

SCHNIERER, S ;

TSCHESCHE, H .

EMBO JOURNAL, 1994, 13 (06) :1263-1269

[7]

SYNTHESIS OF GAMMA-KETO-SUBSTITUTED PHOSPHINIC ACIDS FROM BIS(TRIMETHYLSILYL)PHOSPHONITE AND ALPHA,BETA-UNSATURATED KETONES [J].

BOYD, EA ;

REGAN, AC ;

JAMES, K .

TETRAHEDRON LETTERS, 1992, 33 (06) :813-816

[8]

SYNTHESIS OF ALKYL PHOSPHINIC ACIDS FROM SILYL PHOSPHONITES AND ALKYL-HALIDES [J].

BOYD, EA ;

REGAN, AC ;

JAMES, K .

TETRAHEDRON LETTERS, 1994, 35 (24) :4223-4226

[9]

Phosphinic acid inhibitors of matrix metalloproteinases [J].

Caldwell, CG ;

Sahoo, SP ;

Polo, SA ;

Eversole, RR ;

Lanza, TJ ;

Mills, SG ;

Niedzwiecki, LM ;

IzquierdoMartin, M ;

Chang, BC ;

Harrison, RK ;

Kuo, DW ;

Lin, TY ;

Stein, RL ;

Durette, PL ;

Hagmann, WK .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1996, 6 (03) :323-328

[10]

2 angstrom X-ray structure of adamalysin II complexed with a peptide phosphonate inhibitor adopting a retro-binding mode [J].

Cirilli, M ;

Gallina, C ;

Gavuzzo, E ;

Giordano, C ;

GomisRuth, FX ;

Gorini, B ;

Kress, LF ;

Mazza, F ;

Paradisi, MP ;

Pochetti, G ;

Politi, V .

FEBS LETTERS, 1997, 418 (03) :319-322

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