Biological activity of enzymes

But the term biological model has simpler and cleaner connotation, which actually corresponds more closely to the philological meaning of the word model . The paradigm is now to look at the biological system in order to obtain a hint for a new synthetic system. Thus, the construction of synthetic macromolecules as synthetic catalysts based on model enzymes is very interesting and useful from the point of view of polymer chemistry, but one should not try to use them the other way round, i. e. to obtain information about the catalytic and biological activity of enzymes. 

The presence of surfactants in drug formulations may produce unwanted side or toxic effects because of their interaction with proteins, lipids, membranes and enzymes. To fully understand these interactions, it is essential to have information on the metabolic fate of the ingested surfactant. Membrane disruption by surfactants involves binding of the surfactant monomers to the membrane components, followed by the formation of co-micelles of the surfactant with segments of the membrane. The interaction between surfactants and proteins can lead to solubilization of the insoluble-bound protein or to changes in the biological activity of enzyme... 

Similar particulate systems with a polyelectrolyte polymer core have been developed for the immobilisation of nanoparticles and enzymes (Lu et al, 2009b). In both cases the core of the particles was used for stabilising the catalytic systems, preventing their agglomeration and for easier handling and recovery after the completion of the reaction. In the case of the enzymes, polyelectrolyte polymer core particles present a better way of enzyme immobilisation than immobilisation on solid surfaces. The mild conditions inside the poly electrolyte core preserve the native conformation and biological activity of enzymes. 

Dye-sensitized photooxidation with visible light to identify residues critically involved in the biological activity of enzymes has been introduced by Weil et al. (425). The procedure is mild and moderately selective for some amino acid side chains in addition to tryptophan, tyrosine, histidine, methionine, cysteine and cystine are also photooxidizable. It has been found possible, by an appropriate choice of dye, to bring about specific modification of a particular residue. There is, however, considerable variation in the effects of different dyes and of particular experimental conditions [see ref. 112, 255, 319, 426) for reviews]. 

Quantitative Structure—Activity Relationships (QSAR). Quantitative Stmcture—Activity Relationships (QSAR) is the name given to a broad spectmm of modeling methods which attempt to relate the biological activities of molecules to specific stmctural features, and do so in a quantitative manner (see Enzyme INHIBITORS). The method has been extensively appHed. The concepts involved in QSAR studies and a brief overview of the methodology and appHcations are given here. 

The biological activity of penicillins and cephalosporins is due to the presence of the strained /3-lactam ring, which reacts with and deactivates the transpeptidase enzyme needed to synthesize and repair bacterial cell walls. With the wall either incomplete or weakened, the bacterial cell ruptures and dies. 

Stereoselectivity, in particular, enantioselectivity, is the most important feature of enzymes. It should be stressed that enzymes are capable of recognizing any type of chirality of the substrates. It does not seem necessary to prove here how important the synthesis of sterically defined products is, because the differences in biological activity of particular stereoisomers of a given substance are well known. There are three approaches to the synthesis of enantiomerically enriched... 

There is considerable experimental evidence indicating loss of biological activity of macromolecules such as globular proteins and enzymes at gas-Hquid [57], liquid-solid (Fig. 26) [107] and liquid-liquid [108] interfaces. The extent of inactivation has been shown to be strongly influenced by the prevailing flow field and by, many other factors including the presence and/or absence of additives and contaminants and the type of solid surfaces (Figs. 27 and 28) [107]. 

In each of the assays of potency the amount of the immunoglobulin and the amount of a corresponding standard preparation that are required to neutralize the infectivity or other biological activity of a defined amount of virus or to neutralize a defined amount of a bacterial toxin are determined. The two determined amounts and the assigned unitage of the standard preparation are then used to calculate the potency of the immunoglobulin in International Units (lU). ELISA, enzyme-linked immunosorbent assay. 

The high catalytic activity of enzymes has a number of sources. Every enzyme has a particular active site configured so as to secure intimate contact with the substrate molecule (a strictly defined mutual orientation in space, a coordination of the electronic states, etc.). This results in the formation of highly reactive substrate-enzyme complexes. The influence of tfie individual enzymes also rests on the fact that they act as electron shuttles between adjacent redox systems. In biological systems one often sees multienzyme systems for chains of consecutive steps. These systems are usually built into the membranes, which secures geometric proximity of any two neighboring active sites and transfer of the product of one step to the enzyme catalyzing the next step. 

The biological activity of a compound can often be affected dramatically by the presence of even a single fluorine substituent that is placed in a particular position within the molecule. There are diverse reasons for this, which have been discussed briefly in the preface and introduction of this book. A few illustrative examples of bioactive compounds containing a single fluorine substituent are given in Fig. 3.1. These include what is probably the first example of enhanced bioactivity due to fluorine substitution, that of the corticosteroid 3-1 below wherein Fried discovered, in 1954, that the enhanced acidity of the fluorohydrin enhanced the activity of the compound.1 Also pictured are the antibacterial (3-fluoro amino acid, FA (3-2), which acts as a suicide substrate enzyme inactivator, and the well-known anti-anthrax drug, CIPRO (3-3). 

The activity of many enzymes is pH-dependent because the enzyme may ionize in solution and the biological activity of unionized and ionized forms may be different. In this case, the rate of an enzyme-mediated reaction can be expected to depend on the acidity of the solution. If the enzyme can lose more than one proton as the pH increases (Figure 8.12), the rate of reaction as a function of pH may display a maximum if the forms of the enzyme in strongly acidic or strongly basic solution are inactive, but the intermediate, monoanion, is active. An example of this behavior is provided by fumarase (Figure 8.13). 

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