Enzyme inhibitors polymers, based

Enzyme-sensitive supramolecular polymers also hold promise in analytical applications such as the screening of enzyme inhibitors. A simple visual assay based on the hydrogelation of small molecules has been developed for screening the activities of inhibitors of enzymes like acid phosphatase. A number of inhibitors for... 

In AChE-based biosensors acetylthiocholine is commonly used as a substrate. The thiocholine produced during the catalytic reaction can be monitored using spectromet-ric, amperometric [44] (Fig. 2.2) or potentiometric methods. The enzyme activity is indirectly proportional to the pesticide concentration. La Rosa et al. [45] used 4-ami-nophenyl acetate as the enzyme substrate for a cholinesterase sensor for pesticide determination. This system allowed the determination of esterase activities via oxidation of the enzymatic product 4-aminophenol rather than the typical thiocholine. Sulfonylureas are reversible inhibitors of acetolactate synthase (ALS). By taking advantage of this inhibition mechanism ALS has been entrapped in photo cured polymer of polyvinyl alcohol bearing styrylpyridinium groups (PVA-SbQ) to prepare an amperometric biosensor for... 

Affinity chromatography, based on biological recognition, has become a major means for the purification of biologically active molecules 2). The technique provides a simple and effective way of purification. Specific adsorption of the enzyme to its competitive inhibitor attached to a polymer matrix is the basis for an efficient enzyme purification. Affinity electrophoresis is also based on biological recognition3 . 

Inhibitors may behave differently with immobilized enzymes. Polymers may repel like-charged and attract oppositely charged inhibitors. For instance, APase has a stronger affinity for phosphate than for most substrates (Tijssen, 1985). Phosphate may be attracted by a positively charged membrane and phosphate-based buffers should not be used with APase. With product inhibition, the lack of rapid diffusion may inhibit the enzyme more than in the liquid phase. This may be serious in hybridization using APase. On the other hand, substrate inhibition, such as for peroxidase by H2O2, may be lowered by a restricted diffusion. Changes in the substrate or... 

Several approaches to the photoregulation of proteins have been employed, including photoisomerizable ligands and inhibitors, casting the protein inside a photoisomerizable polymer, and chemical modification of the protein itself [136], Several azobenzene protein effectors have been reported to act as photoregulators of enzymes and receptors. Photoregulation of cysteine and serine proteases was carried out using simple photoswitchable inhibitors which block the active site in their trans form only [137]. Conversely, the cis isomers of a-ketoester-based inhibitors were more potent inhibitors of a-chymotrypsin than the trans forms... 

A convergent synthesis of the potent selective inhibitor of the enzyme phosphodiesterase sildenafil (Viagra) has been based on polymer supported reagents [134], In this synthesis, the HOBt-supported resin 126 has been used for the isolation and preparation of the resin-bound active ester 128, performed by coupling polymer 126 with the benzoic acid sulfonamide derivative 127 by means of PyBrop (Scheme 7.40). Subsequent reaction of active ester 128 with aminopyrazole 129 gave rise to the clean synthesis of amide 130, which has been transformed into sildenafil (131) after a base-promoted pyrimidinone formation. 

Although the use of a model has led to greater understanding of polymer dynamics, it is more satisfactory to obtain motional amplitudes and rates directly from the relaxation data. A general formalism for performing this reduction, based on the theory of Markov processes, has been described by King et al. The mdhod has not as yet been applied to synthetic polymers, but the valuable insights obtained by its application to the enzyme bovine pancreatic trypsin inhibitor demonstrate its potential. 

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