Chemically reactive immunogens lead to functional convergence of the immune response

被引:14
作者
Shulman, H
Makarov, C
Ogawa, AK
Romesberg, F
Keinan, E [1 ]
机构
[1] Technion Israel Inst Technol, Dept Chem, IL-32000 Haifa, Israel
[2] Technion Israel Inst Technol, Inst Catalysis Sci & Technol, IL-32000 Haifa, Israel
[3] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA
[4] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA
关键词
D O I
10.1021/ja000616o
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
An aldolase antibody, 24H6, which was obtained from immunization with the large hapten 2, is shown to possess an active-site lysine residue with a perturbed pK(a) of 7.0. This antibody catalyzes both the aldol addition and the retrograde aldol fragmentation with a broad range of substrates that are structurally different from the hapten. This observation suggests that in reactive immunization with 1,3-diketones, the hapten structure governs the chemistry but not the overall organization of the active site. Hammett correlation studies of the 38C2- and 24H6-catalyzed aldol and retroaldol reactions revealed that although the two antibodies exhibit broad substrate specificities, they utilize slightly different mechanisms. While antibody 38C2 adopts a mechanism that is reminiscent of an acid-catalyzed aldol reaction, antibody 24H6 follows a mechanism that is similar to the base-catalyzed reaction.
引用
收藏
页码:10743 / 10753
页数:11
相关论文
共 71 条
[1]  
[Anonymous], 2001, The Immune System in Health and Disease
[2]  
[Anonymous], 1986, Monoclonal Antibodies: Principles and Practice
[3]   The mechanism of addition of phenols to tetramesityldisilene. Evidence for both nucleophilic and electrophilic rate-determining steps [J].
Apeloig, Y ;
Nakash, M .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1996, 118 (40) :9798-9799
[4]   CATALYTIC ENANTIOSELECTIVE C-C COUPLING - ALLYL TRANSFER AND MUKAIYAMA ALDOL REACTION [J].
BACH, T .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION IN ENGLISH, 1994, 33 (04) :417-419
[5]   SOMATIC MUTATION GAINS ITS PLACE AMONG THE GENERATORS OF DIVERSITY [J].
BALTIMORE, D .
CELL, 1981, 26 (03) :295-296
[6]   Immune versus natural selection: Antibody aldolases with enzymic rates but broader scope [J].
Barbas, CF ;
Heine, A ;
Zhong, GF ;
Hoffmann, T ;
Gramatikova, S ;
Bjornestedt, R ;
List, B ;
Anderson, J ;
Stura, EA ;
Wilson, IA ;
Lerner, RA .
SCIENCE, 1997, 278 (5346) :2085-2092
[7]   ASYMMETRIC ALDOL REACTIONS USING (4R-TRANS)-2-(1-METHYL-ETHENYL)-1,3,2-DIOXABOROLANE-4,5-DICARBOXYLIC ACID, BIS-ETHYL ESTER, A CHIRAL PRECURSOR OF THE ACETONE ENOLATE [J].
BOLDRINI, GP ;
LODI, L ;
TAGLIAVINI, E ;
TROMBINI, C ;
UMANIRONCHI, A .
JOURNAL OF ORGANOMETALLIC CHEMISTRY, 1987, 336 (1-2) :23-28
[8]   CATALYTIC, ENANTIOSELECTIVE ACETONE ALDOL ADDITIONS WITH 2-METHOXYPROPENE [J].
CARREIRA, EM ;
LEE, W ;
SINGER, RA .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1995, 117 (12) :3649-3650
[9]  
CHAPMAN NB, 1978, CORRELATION ANAL CHE, P455
[10]   SINGLE-STEP METHOD OF RNA ISOLATION BY ACID GUANIDINIUM THIOCYANATE PHENOL CHLOROFORM EXTRACTION [J].
CHOMCZYNSKI, P ;
SACCHI, N .
ANALYTICAL BIOCHEMISTRY, 1987, 162 (01) :156-159