Biomolecules enzyme

Drug-discovery process is a highly complex, multidisciplinary and time-consuming procedure, which typically starts from the identification of appropriate drug targets (biomolecules, enzymes, ion channels, receptors) to target validation, where it was established whether the target was of relevance for the disease under study. 

Biosensors include electrodes modified with biomolecules enzymes, DNA, antibodies, vegetable tissue or microorganisms. 

Layer-by-layer (LbL) assembly is a unique technique for the fabrication of composite films with precise thickness control at the nanometer scale [111, 112], The method is based on the alternate adsorption of oppositely charged species from their solutions. The attractive feature of this approach is its ability to assemble complex structures from modular components, and integrate them into self-assembling constructions for a wide range of applications. The LbL method has been successfully exploited in the construction of dendrimer biosensors [113,114], The LbL films provide a favorable environment for the intimate contact between the dendrimer and biomolecule (enzymes or proteins), promoting a direct electron transfer between them and the underlying electrodes. 

The low-temperature nature of the sol-gel process lends itself well to the entrapment of organic materials (dyes, polymers, redox reagents) and biomolecules (enzymes, proteins, antibodies, whole cells) which are immobilized inside an inorganic matrix. This opens up a whole new class of materials with unique properties. This rapidly growing topic has been extensively reviewed in the... 

It has been observed that the surface of the conducting polymer plays an important role in the effective immobilisation of the desired enzyme. The Langmuir-Blodgett (LB) technique can be successfully applied to deposit a desired monolayer with the desired orientation of the biomolecules/enzymes [142-145]. Ramanathan and co-workers [146] have utilised the polyemeraldine base LB films for the immobilisation of GOD. These films have been shown to function as amperometric glucose biosensors and have a linear range from 5 to 50 mM. LB films of PT immobilised with GOD and urease have also been prepared for application to respective biosensors [147, 148]. 

Apart from the sheer complexity of the static stmctures of biomolecules, they are also rather labile. On the one hand this means that especial consideration must be given to the fact (for example in electron microscopy) that samples have to be dried, possibly stained, and then measured in high vacuum, which may introduce artifacts into the observed images [5]. On the other, apart from the vexing question of whether a protein in a crystal has the same stmcture as one freely diffusing in solution, the static stmcture resulting from an x-ray diffraction experiment gives few clues to the molecular motions on which operation of an enzyme depends [6]. 

All chemical reactions, whether in the laboratory or in living organisms, follow the same "rules." Reactions in living organisms often look more complex than laboratory reactions because of the size of the biomolecules and the involvement of biological catalysis called enzymes, but the principles governing all reactions are the same. 

The search for inhibitors of this pathway began with the first key regulatory enzyme, HMG CoA reductase. Several clinically useful inhibitors of HMG CoA reductase are now known. One of the most successful, Mevacor, produced by Merck, is one of the pharmaceutical industry s best selling products. However, the problem with inhibiting a branched biosynthetic pathway at an early point is that the biosynthesis of other crucial biomolecules may also be inhibited. Indeed, there is some evidence that levels of ubiquinone and the dolichols are affected by some HMG CoA reductase inhibitors. Consequently, efforts have recently been directed towards finding inhibitors of squalene synthase, the enzyme controlling the first step on the route to cholesterol after the FPP branch point. 

If we consider natural synthetic processes, enzymes are seen to exert complete control over the enantiomeric purity of biomolecules (see Figure 8.2). They are able to achieve this because they are made of single enantiomers of amino adds. The resulting enantiomer of the enzymes functions as a template for the synthesis of only one enantiomer of the product Moreover, the interaction of an enzyme with the two enantiomers of a given substrate molecule will be different. Biologically important molecules often show effective activity as one enantiomer, the other is at best ineffective or at worst detrimental. 

Basic technology for membrane separation of biomolecules was invented in the United States, but the West Germans and the Japanese lead in its application to separations of enzymes and amino acids from complex mixtures. Japanese... 

The synthesis of glycoconjugates opens the route to one of the most important class of biomolecules which play an active role in relevant biological reactions [26]. One way to do so is to use enzymes, which, however, suffer from instability and slow reaction rates. 

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