Intercalated enzyme molecules

A second application of the index is its use to predict candidate molecules to fill molecular cavities. With the increasing use of molecular graphics, the fit, docking, or intercalation of molecules into cavities in macromolecular simulations becomes an important consideration in drug design. The visualizations of proposed receptor sites, enzyme active sites, and other cavities and spaces of interest in macromolecules make it possible to make measurements of the dimensions of a cavity. Of course, the validity of these images depends on the quality of the input data and the assumptions attending the calculations. If the visualized details of a cavity are to be believed, then there is certainly some interest in what molecules may fit that cavity or some part of it. 

When supported complexes are the catalysts, two types of ionic solid were used zeolites and clays. The structures of these solids (microporous and lamellar respectively) help to improve the stability of the complex catalyst under the reaction conditions by preventing the catalytic species from undergoing dimerization or aggregation, both phenomena which are known to be deactivating. In some cases, the pore walls can tune the selectivity of the reaction by steric effects. The strong similarities of zeolites with the protein portion of natural enzymes was emphasized by Herron.20 The protein protects the active site from side reactions, sieves the substrate molecules, and provides a stereochemically demanding void. Metal complexes have been encapsulated in zeolites, successfully mimicking metalloenzymes for oxidation reactions. Two methods of synthesis of such encapsulated/intercalated complexes have been tested, as follows. 

Clay minerals or phyllosilicates are lamellar natural and synthetic materials with high surface area, cation exchange and swelling properties, exfoliation ability, variable surface charge density and hydrophobic/hydrophilic character [85], They are good host structures for intercalation or adsorption of organic molecules and macromolecules, particularly proteins. On the basis of the natural adsorption of proteins by clay minerals and various clay complexes that occurs in soils, many authors have investigated the use of clay and clay-derived materials as matrices for the immobilization of enzymes, either for environmental chemistry purpose or in the chemical and material industries. 

Several molecules displaying antitumour properties are efficient electron acceptors. Besides their ability to intercalate between DNA base pairs they can be reduced by enzymes. 5 /Y- Pyridophenoxazin-5-one (21) is a new anticancer iminoquinone which exhibits such properties. It can be readily reduced to its radical anion (Em = -0.496 V vs. NHE) with a delocalized structure it is able to form Cu(II) complexes and acts as a mediator for the formation of superoxide radical anions243. 

Distorting the planarity of the molecule by introducing bulky groups ortho to the inter-cyclic linkages decreases ability to intercalate DNA and makes it a poor substrate for activation enzymes... 

How do antibiotics act Some, like penicillin, block specific enzymes. Peptide antibiotics often form complexes with metal ions (Fig. 8-22) and disrupt the control of ion permeability in bacterial membranes. Polyene antibiotics interfere with proton and ion transport in fungal membranes. Tetracyclines and many other antibiotics interfere directly with protein synthesis (Box 29-B). Others intercalate into DNA molecules (Fig. 5-23 Box 28-A). There is no single mode of action. The search for suitable antibiotics for human use consists in finding compounds highly toxic to infective organisms but with low toxicity to human cells. 

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