Tables enzyme inhibitors

Nucleophilic addition reactions to A -monoprotected a-amino aldehydes 1 (Table 20) represent the beginning of the worldwide interest in peptide isosteres for the preparation of certain specific enzyme inhibitors (e.g., aspartylproteinase inhibition). Some examples of this reaction type show a relatively low diastereofacial selectivity, especially when the reactions are per-... 

Table 1.1 Selected enzyme inhibitors in clinical use or trials...

Table 3.2 Some examples of competitive enzyme inhibitors in clinical use...

Table 5.1 Characteristic effects of substrate concentration on the IC50 value for reversible enzyme inhibitors of different modalities...

Table 6.1 Some examples of slow binding enzyme inhibitors...

Table 7.2 Three zones of enzyme-inhibitor interactions defined by Strauss and Goldstein (1943)...

Let us assume that for a particular enzyme-inhibitor pair, association is diffusion limited so that k, is I O9 M s1. Fixing k n at this value, and using Equation (7.26), we can determine the value of koB for different values of Kn as summarized in Table 7.3 (this is taken from the more comprehensive table presented in Chapter 2). We have already seen examples in Chapter 6 of compounds with A) values (or Kf values) in the lOnM to lOpM range for which the half-life for binary complex dissociation is far longer than 2 hours. For example, we saw that inhibition of COX2 by DuP697 resulted in a final E I complex with Kf = 5 nM and the lm for complex... 

Table 7.3 Values of k for different values for enzyme-inhibitor binary complexes when the rate of complex association is diffusion-limited (k = I09M W)...

To close on a more positive note, we observe that the computed geometry of the enzyme-dienolate complex in the vicinity of the 3-carbonyl is insensitive to the assumed dielectric constant and is in close agreement with X-ray structures of enzyme-inhibitor complexes (see Table 4.11 and Fig. 4.15). It is really quite remarkable that 4 billion years of random walk by mother nature and a few hours of optimization with a quantum chemistry program such as Gaussian (starting with the correct functional groups) lead to the same structure for the active... 

VIII. Table of PDB-Entries Enzyme-Inhibitor Complexes of Imino Sugars and Selected... 

Heparin has been found to bind a large number of proteins (Table 3). The biological activity of heparin and related polysaccharides is usually ascribed to their interaction with heparin-binding proteins. These proteins can be classified into classes including (1) enzymes, (2) protease inhibitors, (3) lipoproteins, (4) growth factors, (5) chemokines, (6) selectins, (7) extracellular matrix proteins, (8) receptor proteins, (9) viral coat proteins, (10) nuclear proteins, and (11) other proteins (1). Many heparin-binding proteins are enzymes and enzyme inhibitors. For example, proteases in the coagulation cascade, such as factors Ha, IXa, Xa, Xlla, and Villa, are heparin-... 

Table 6. Some enzyme inhibitors frequently impUcated in interactions...

Complementary structures of biological materials, especially those of proteins, often result in specific recognitions and various types of biological affinity. These include many pairs of substances, such as enzyme-inhibitor, enzyme-substrate (analog), enzyme-coenzyme, hormone-receptor, and antigen-antibody, as summarized in Table 11.2. Thus, bioaffinity represents a useful approach to separating specific biological materials. 

Table 5.27 Effect of the Enzyme Inhibitor Triacetyloleandomycin on Metabolism of Hexobarbital...

As illustrated by the examples in Table 15.30, diketopiperazines are amenable to many structural variations. These heterocycles thus seem to be well suited for the preparation of libraries for lead discovery, and have, for instance, been used for the identification of new enzyme inhibitors [368]. Libraries of diketopiperazines will, however, be sparsely diverse because the diketopiperazine ring itself is pharmacophore-rich , and will contribute significantly to the overall properties of all the members of the library (see Section 1.4). 

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