Synthetic artificial peptidases and nucleases using macromolecular catalytic systems

被引:171
作者
Suh, J [1 ]
机构
[1] Seoul Natl Univ, Sch Chem, Seoul 151747, South Korea
[2] Seoul Natl Univ, Ctr Mol Catalysis, Seoul 151747, South Korea
关键词
D O I
10.1021/ar020037j
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Effective artificial enzymes have been designed by adopting macromolecular systems for catalyst-substrate complexes. Artificial active sites comprising two or more organic functional groups were built on macromolecutar backbones, leading to several types of organic artificial proteases. The activity of metal centers for peptide or DNA hydrolysis was greatly enhanced by attachment to polystyrene, leading to artificial metallopeptidases with substrate selectivity as well as artificial metallonucleases with high catalytic activity for double stranded DNA. A small artificial protease selective for a macromolecular target protein was synthesized. Target-specific artificial proteases can be used as protein-cleaving catalytic drugs.
引用
收藏
页码:562 / 570
页数:9
相关论文
共 67 条
[31]   EFFICIENT AND OXYGEN-INDEPENDENT HYDROLYSIS OF SINGLE-STRANDED-DNA BY CERIUM(IV) ION [J].
KOMIYAMA, M ;
TAKEDA, N ;
TAKAHASHI, Y ;
UCHIDA, H ;
SHIIBA, T ;
KODAMA, T ;
YASHIRO, M .
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2, 1995, (02) :269-274
[32]   AT THE CROSSROADS OF CHEMISTRY AND IMMUNOLOGY - CATALYTIC ANTIBODIES [J].
LERNER, RA ;
BENKOVIC, SJ ;
SCHULTZ, PG .
SCIENCE, 1991, 252 (5006) :659-667
[33]   Catalysis of phosphodiester transesterification by dinuclear Cu(II) complexes: The role of the second Cu(II) ion [J].
Liu, SH ;
Hamilton, AD .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1997, 7 (13) :1779-1784
[34]   ORIGIN OF RATE ACCELERATIONS IN AN ENZYME MODEL - THE PARA-NITROPHENYL ESTER SYNDROME [J].
MENGER, FM ;
LADIKA, M .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1987, 109 (10) :3145-3146
[35]   Efficient catalytic phosphate diester cleavage by the synergetic action of two Cu(II) centers in a dinuclear cis-diaqua Cu(II) calix[4]arene enzyme model [J].
Molenveld, P ;
Engbersen, JFJ ;
Kooijman, H ;
Spek, AL ;
Reinhoudt, DN .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1998, 120 (27) :6726-6737
[36]   Artificial trinuclear metallopeptidase synthesized by cross-linkage of a molecular bowl with a polystyrene derivative [J].
Moon, SJ ;
Jeon, JW ;
Kim, H ;
Suh, MP ;
Suh, J .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2000, 122 (32) :7742-7749
[37]   An aspartic protease analogue: Intermolecular catalysis of peptide hydrolysis by carboxyl groups [J].
Oh, S ;
Chang, W ;
Suh, J .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (11) :1469-1472
[38]   Ab initio studies on the catalytic mechanism of aspartic proteinases: Nucleophilic versus general acid/general base mechanism [J].
Park, H ;
Suh, J ;
Lee, S .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2000, 122 (16) :3901-3908
[39]   Rates of uncatalyzed peptide bond hydrolysis in neutral solution and the transition state affinities of proteases [J].
Radzicka, A ;
Wolfenden, R .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1996, 118 (26) :6105-6109
[40]   TRANSFER OF OXYGEN FROM AN ARTIFICIAL PROTEASE TO PEPTIDE CARBON DURING PROTEOLYSIS [J].
RANA, TM ;
MEARES, CF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (23) :10578-10582