Biotechnology and combinatorial chemistry
In modern drug research is the development of rapid methods for screening for substrate specificity and inhibition of proteolytic enzymes important, which requires a deep understanding of several interdisciplinary techniques. Multi-resistant bacteria such as DT-104, TB and mutant viruses (HIV) requires constant focus more on rational ether design and new concepts for drug development. Read the original article here
Proteolytic enzymes are involved in viral, bacterial and parasitic infections, ether and are therefore interesting target for the development of new potential drugs. The human genome ether has now been mapped and codes for more than 2000 proteolytic enzymes, and many new genes and proteins with potential pharmaceutical relevance will be identified in the coming years. Combinatorial methods ether can be used to optimize ether the relevant molecules to combat dysfunctional regulated enzymes. This is particularly relevant to viral proteases seem to mutate a combinatorial speed, which confers resistance to known drugs. The development of new resins sensitive analytical methods, assays and solid-phase chemistry, aimed at production of the enzyme inhibitors can be a key means for identification of new drugs against proteolytic enzymes.
Polymer Technology The basis of the techniques developed in the Center for Solid Phase Organic Combinatorial Chemistry (SPOCC) during the Carlsberg Laboratory, polymers with optimized properties for organic synthesis and enzymatic studies. These polymers / resins are compatible with all the solvents, so that both the organic reagents and enzymes are able to penetrate the polymeric network. It is essential, as the majority (> 99%) of the resin-bound molecules located in the interior of the polymer and not on the surface. Polyethylene ether glycol ether (PEG) is the main component of the resins (about 90-95%), it is hydrophilic, inert, and known as a stabilizer of enzymes and proteins. Therefore, the PEG-based resins are ideal for the synthesis of chemical libraries, and subsequent enzymatic screening on solid phase. PEG modified at the ends and polymerized through radical reactions (PEGA, POEPS), anionic (POEPOP) or cationic (SPOCC) ring opening reactions, ether the resins having amino or hydroxy functionalities, which can then be used for organic synthesis [1,2]. The resins are polymerized as droplets in silicone oil, and by rapid stirring, the particle size is controlled, and spherical particles with a diameter in the range of from 10 mm to 1000 mm can be produced. [3] Each resin may act as a chemical micro reactor with a limited volume in which either organic reagents or enzymes to operate. This principle can include used for the preparation of combinatorial libraries on solid phase.
Combinatorial libraries Proteolytic enzymes are generally involved ether in viruses, bacterial, and parasitic infections. They represent an attractive target in pharmaceutical research and development of specific enzyme inhibitors is still a major challenge ether in the pharmaceutical industry. In order to perform enzymatic assays on solid phase enzyme have free access to substrate throughout the polymer network, and the enzyme to remain active. PEG-based resins have been found to be ideal polymers, and satisfy the conditions of peptide synthesis, several organic reactions and enzymatic interactions on the solid phase. Proteolytic enzymes are characterized by their degradation of substrates through an enzyme-substrate complex is cleaved into a finished product. Use of a combinatorial library of potential substrates may, in principle, identify any enzyme substrate. The 'split-and-mix' approach developed by Furka [4] peptide substratbiblioteker ether (also called "one-bead-one-compound 'libraries) with great diversity produced in a short time. Proteolytic cleavage of the substrate bound to the resin is detected by using a fluorescent group (Abz) that "quenched" in the presence of a covalently bound Tyr (NO 2) [5]. By enzymatic cleavage of the substrate is released Tyr (NO2) from the resin, which resins with active substrate will fluoresce and identifiable on visual selection. Solid phase combinatorial libraries of peptides have been widely used for the characterization of proteolytic enzymes such as subtilisin Carlsberg, trypsin, cysteine proteases, matrix metalloproteinases and Others Characterization of an enzyme substrate specificity is important in view of the discovery of new enzyme inhibitors.
Peptido-organic libraries to identify enzyme inhibitors By combining the high potential of combinatorial chemistry with peptide and organic synthesis on solid phase, a centrally located inhibitorelement omgrænses of amino acids. Many organic reactions has been transferred to the solid phase, but only a limited number are quantitative so that the view of the combinatorial libraries can be used in which the active components ether are analyzed by mass spectrometry or
In modern drug research is the development of rapid methods for screening for substrate specificity and inhibition of proteolytic enzymes important, which requires a deep understanding of several interdisciplinary techniques. Multi-resistant bacteria such as DT-104, TB and mutant viruses (HIV) requires constant focus more on rational ether design and new concepts for drug development. Read the original article here
Proteolytic enzymes are involved in viral, bacterial and parasitic infections, ether and are therefore interesting target for the development of new potential drugs. The human genome ether has now been mapped and codes for more than 2000 proteolytic enzymes, and many new genes and proteins with potential pharmaceutical relevance will be identified in the coming years. Combinatorial methods ether can be used to optimize ether the relevant molecules to combat dysfunctional regulated enzymes. This is particularly relevant to viral proteases seem to mutate a combinatorial speed, which confers resistance to known drugs. The development of new resins sensitive analytical methods, assays and solid-phase chemistry, aimed at production of the enzyme inhibitors can be a key means for identification of new drugs against proteolytic enzymes.
Polymer Technology The basis of the techniques developed in the Center for Solid Phase Organic Combinatorial Chemistry (SPOCC) during the Carlsberg Laboratory, polymers with optimized properties for organic synthesis and enzymatic studies. These polymers / resins are compatible with all the solvents, so that both the organic reagents and enzymes are able to penetrate the polymeric network. It is essential, as the majority (> 99%) of the resin-bound molecules located in the interior of the polymer and not on the surface. Polyethylene ether glycol ether (PEG) is the main component of the resins (about 90-95%), it is hydrophilic, inert, and known as a stabilizer of enzymes and proteins. Therefore, the PEG-based resins are ideal for the synthesis of chemical libraries, and subsequent enzymatic screening on solid phase. PEG modified at the ends and polymerized through radical reactions (PEGA, POEPS), anionic (POEPOP) or cationic (SPOCC) ring opening reactions, ether the resins having amino or hydroxy functionalities, which can then be used for organic synthesis [1,2]. The resins are polymerized as droplets in silicone oil, and by rapid stirring, the particle size is controlled, and spherical particles with a diameter in the range of from 10 mm to 1000 mm can be produced. [3] Each resin may act as a chemical micro reactor with a limited volume in which either organic reagents or enzymes to operate. This principle can include used for the preparation of combinatorial libraries on solid phase.
Combinatorial libraries Proteolytic enzymes are generally involved ether in viruses, bacterial, and parasitic infections. They represent an attractive target in pharmaceutical research and development of specific enzyme inhibitors is still a major challenge ether in the pharmaceutical industry. In order to perform enzymatic assays on solid phase enzyme have free access to substrate throughout the polymer network, and the enzyme to remain active. PEG-based resins have been found to be ideal polymers, and satisfy the conditions of peptide synthesis, several organic reactions and enzymatic interactions on the solid phase. Proteolytic enzymes are characterized by their degradation of substrates through an enzyme-substrate complex is cleaved into a finished product. Use of a combinatorial library of potential substrates may, in principle, identify any enzyme substrate. The 'split-and-mix' approach developed by Furka [4] peptide substratbiblioteker ether (also called "one-bead-one-compound 'libraries) with great diversity produced in a short time. Proteolytic cleavage of the substrate bound to the resin is detected by using a fluorescent group (Abz) that "quenched" in the presence of a covalently bound Tyr (NO 2) [5]. By enzymatic cleavage of the substrate is released Tyr (NO2) from the resin, which resins with active substrate will fluoresce and identifiable on visual selection. Solid phase combinatorial libraries of peptides have been widely used for the characterization of proteolytic enzymes such as subtilisin Carlsberg, trypsin, cysteine proteases, matrix metalloproteinases and Others Characterization of an enzyme substrate specificity is important in view of the discovery of new enzyme inhibitors.
Peptido-organic libraries to identify enzyme inhibitors By combining the high potential of combinatorial chemistry with peptide and organic synthesis on solid phase, a centrally located inhibitorelement omgrænses of amino acids. Many organic reactions has been transferred to the solid phase, but only a limited number are quantitative so that the view of the combinatorial libraries can be used in which the active components ether are analyzed by mass spectrometry or
