Big Chemical Encyclopedia

Chemical substances, components, reactions, process design ...

Articles Figures Tables About

Some Catalytic Antibodies

The creation of the first catalytic antibodies by Richard A. Lerner and Peter G. Schultz (both of Scripps Research Institute) represented an ingenious union of principles relating to enzyme chemistry and the innate capabilities of the immune system. In some respects catalytic antibodies are like enzymes, the protein catalysts we have mentioned many times already and shall study further in this chapter. Unlike enzymes, however, catalytic antibodies can virtually be "made to order" for specific reactions by a marriage of chemistry and immunology. Examples include catalytic antibodies for Claisen rearrangements, Diels-Alder reactions (such as that shown in the molecular graphic above), ester hydrolyses, and aldol reactions. We shall consider how catalytic antibodies are produced in "The Chemistry of... Some Catalytic Antibodies" later in this chapter. Designer catalysts are indeed at hand. [Pg.1084]

There is another approach that is increasingly part of synthesis the use of enzymes as catalysts. This approach is strengthened by the new ability of chemists and molecular biologists to modify enzymes and change their properties. There is also interest in the use of artificial enzymes for this purpose, either those that are enzyme-like but are not proteins, or those that are proteins but based on antibodies. Catalytic antibodies and nonprotein enzyme mimics have shown some of the attractive features of enzymes in processes for which natural enzymes are not suitable. [Pg.32]

In Figure 3 a schematic view is presented of how primary catalysis is achieved. Besides this necessary and sufficient condition required to set up catalysis, there may be some other factors producing an enhancement of the catalytic event. General acid and general base catalytic groups, metal coordination sphere appropriately prepared are examples of catalytic subsidiary effects. The pure molding factor is usually achieved by catalytic antibodies techniques. [Pg.333]

At the end of the review there are some examples involving catalysis by acids and bases, metal ions, micelles, amylose, catalytic antibodies, and enzymes to give the reader a feeling for how Kurz s approach may be usefully applied to other catalysts. Very few of these examples, or those involving cyclodextrins, were discussed in the original literature in the same terms. It is hoped that the present treatment will stimulate further use and exploration of the Kurz approach to analysing transition state stabilization. [Pg.3]

A second use of this type of analysis has been presented by Stewart and Benkovic (1995). They showed that the observed rate accelerations for some 60 antibody-catalysed processes can be predicted from the ratio of equilibrium binding constants to the catalytic antibodies for the reaction substrate, Km, and for the TSA used to raise the antibody, Kt. In particular, this approach supports a rationalization of product selectivity shown by many antibody catalysts for disfavoured reactions (Section 6) and predictions of the extent of rate accelerations that may be ultimately achieved by abzymes. They also used the analysis to highlight some differences between mechanism of catalysis by enzymes and abzymes (Stewart and Benkovic, 1995). It is interesting to note that the data plotted (Fig. 17) show a high degree of scatter with a correlation coefficient for the linear fit of only 0.6 and with a slope of 0.46, very different from the theoretical slope of unity. Perhaps of greatest significance are the... [Pg.280]

Many of the 60 known reactions catalyzed by monoclonal antibodies involve kinetically favored reactions e.g., ester hydrolysis), but abzymes can also speed up kinetically disfavored reactions. Stewart and Benkovic apphed transition-state theory to analyze the scope and limitations of antibody catalysis quantitatively. They found the observed rate accelerations can be predicted from the ratio of equilibrium binding constants of the reaction substrate and the transition-state analogue used to raise the antibody. This approach permitted them to rationalize product selectivity displayed in antibody catalysis of disfavored reactions, to predict the degree of rate acceleration that catalytic antibodies may ultimately afford, and to highlight some differences between the way that they and enzymes catalyze reactions. [Pg.115]

The nature of antibody catalysis remains to be elucidated, and antibodies will not reach the efficiency of enzymes until they can emulate the conformational changes, acid/base, redox, and/or nucleophilic/electro-philic reactivities of catalytic residues along the entire reaction coordinate. It is worthy of note that Hollfelder et al recently demonstrated that serum albumins catalyze the eliminative ring-opening of a benzoisoxazole at rates that are similar to those observed with catalytic antibodies. They suggest that formal general base catalysis contributes only modestly to the efficiency of both systems, and they favor the view that the antibody catalysis may be enhanced in some cases by nonspecific medium effects. [Pg.115]

Both enzymes and antibodies are proteins. Antibodies consist of subunits with multiple domains, just as do some enzymes. Both enzymes and antibodies have binding sites for small molecules between domains or subunits. In view of such similarities it isn t surprising that some antibodies have catalytic properties. The possibility was suggested in 1969 by Jencks 3 He also proposed that injection of a mouse with a hapten, that resembled a transition state for an enzyme, might induce formation of antibodies complementary to the transition-state structure. These might be catalytic. By the early 1980s such antibodies were discovered.1 d Some of the first catalytic antibodies (also dubbed abzymes) had esterase activity. The haptens used to induce antibody formation were phosphonates such as the following.e f... [Pg.1842]

Using the transition-state analog shown on p. 485 a catalytic antibody with chorismate mutase activity was isolated. Many antibodies catalyzing additional reactions have also been found. Although they are usually less active than natural enzymes, in some cases they approach enzymatic rates. Furthermore, they may catalyze reactions for which no known enzymes exist.h... [Pg.1842]

Two different approaches, catalytic antibodies (Ab) and molecularly imprinted polymers (MIPs), have been investigated with the aim of achieving this target and the next section will provide some general outlines. [Pg.308]

Catalytic antibodies, predicted by Jencks in 1969 and first discovered in 1986, can now be raised against a wide variety of haptens covering nearly every reaction. Catalytic antibodies are regarded as the best enzyme mimics, with very good selectivity, but almost always their catalytic efficiency is by far insufficient. Some natural RNA molecules act as catalysts with intrinsic enzyme-like activity which permits them to catalyze chemical reactions in the complete absence of protein cofactors. In addition, ribozymes identified through in-vitro selection have extended the repertoire of RNA catalysis. This versatility has lent credence to the idea that RNA molecules may have been central to the early stages of life on Earth. [Pg.511]

Naturally occurring redox enzymes have been successfully exploited for asymmetric synthesis for some years.1 Although impressive chemo-, regio-, and enantioselectivities have been achieved in some cases, these biocatalysts have prescribed selectivity and often require expensive cofactors that must be recycled for preparative work. Catalytic antibodies offer an attractive alternative, since they are not limited a priori by Nature s choices. Thus the need for cofactor recycling can be circumvented through the use of inexpensive oxidants and reductants, and, as we have seen above, selectivity can be tailored through appropriate hapten design. [Pg.120]

In this section is an overview of some historical aspects of enzyme studies with special emphasis on new methods of purification, structure determination, and research on the reaction mechanism of an enzyme. Enzyme application for medical and industrial use and development of novel enzymes such as catalytic RNA (ribozyme) and catalytic antibody (abzymes) are also briefly described. [Pg.4]

The availability of 38C2 as a broad scope, enantioselective, efficient aldolase enzyme has had a significant impact on organic synthesis. Some of the molecules we have synthesized with 38C2 include the natural products ( + ) —frontalin [( + )— 27] (List et al., 1999), some brevicomins [( —) —28 and (—) —29] (List etal., 1998a), epothilones A (30) and C (31) (Sinha et al., 1998), and the Wieland-Miescher ketone [( ) — ( + )—32] (Hoffmann et al., 1998 Zhong et al., 1997). The brevicomin examples represent the first use of a catalytic antibody to decrease the total number of synthetic steps and increase the enantioselectivity of natural product syntheses. [Pg.338]

Similar to catalytic antibodies, we observed some product inhibition. In the case mentioned, the reaction rate was calculated from the amount of released acid. If the calculation is based on phenol release, the rate enhancement turned out to be nearly doubled. Hydrolysis of carbonates should avoid this difficulty. Therefore, diphenyl phosphate was used as template, and the hydrolysis of diphenyl carbonate was then investigated [13]. Compared to solution an enhancement of 982-fold was obtained and typical Michaelis-Menten kinetics were observed (K ,ax = 0.023 mM/min, = 5.01 mM, = 0.0115/min, kaalK = 2.30/min/M). [Pg.105]

Catalytic antibodies were first prepared in the mid-1980s. In one example, a rabbit or mouse was immunized with phosphonate ester A, and pure anti-A antibodies were isolated from this animal s spleen cells. Some of the anti-A antibodies were found to catalyze the hydrolysis of the ester functionality of B at rates significantly faster than background. [Pg.104]


See other pages where Some Catalytic Antibodies is mentioned: [Pg.352]    [Pg.1017]    [Pg.1206]    [Pg.1209]    [Pg.1041]    [Pg.1123]    [Pg.352]    [Pg.352]    [Pg.1017]    [Pg.1206]    [Pg.1209]    [Pg.1041]    [Pg.1123]    [Pg.352]    [Pg.206]    [Pg.309]    [Pg.324]    [Pg.335]    [Pg.349]    [Pg.266]    [Pg.116]    [Pg.221]    [Pg.519]    [Pg.206]    [Pg.308]    [Pg.457]    [Pg.127]    [Pg.58]    [Pg.385]    [Pg.89]    [Pg.103]    [Pg.83]    [Pg.90]    [Pg.120]    [Pg.206]    [Pg.828]    [Pg.145]    [Pg.145]    [Pg.159]   


SEARCH



Antibodies catalytic

THE CHEMISTRY OF. .. Some Catalytic Antibodies

© 2024 chempedia.info