For years, the structure, function and dynamics of proteins have intrigued biochemists and chemists and inspired the design of targeted low molecular weight drugs. Today, as biotechnology progresses, proteins are themselves being used in the treatment of several diseases. Almost every gene can now be cloned and its protein product produced in any expression system depending on the desired folding, stability, post-translational modification, cost of production and ease of recovery. An increase in the isolation of large volumes of recombinant proteins such as antibodies, antrivirals, cytokines, enzymes, clotting factors and vaccines for therapeutic, diagnostic and research purposes has made efficient protein purification the most important step in the recovery of efficacious and fully active biopharmaceuticals.

All steps in the production of biopharmaceuticals need to be compliant with the safety guidelines laid out by regulatory authorities such as the US Food and Drug Administration and the equivalent European authority. The final product should be a 'well characterized biologic' with defined major impurities, if any, very low levels of DNA and viruses (less than 10 pg per dose), pyrogens (less than 300 endotoxin units per dose) and leachates from the separation matrices. Table 1 highlights some of the quality control requirements imposed by the regulatory authorities on proteins used for clinical applications. Commonly purified end products are mixtures of isoforms of proteins with variations in post-translational modifications such as glycosylation, oxidation, end terminal alterations, misfolding, incorrect disulfide bridging and nicked or truncated variants. Thus, techniques such as high performance liquid chromatography (HPLC), peptide mapping, capillary electrophoresis, isoelectric focusing, circular dichroism and mass spectrometry are also gaining an impetus in thorough characterization of the potency, purity and safety of protein drugs.

The increasing demand for peptides, nucleotides, low molecular weight synthetic molecules and bio-mimetic ligands for protein purification has inspired chemists to generate focused and general combinatorial libraries of diverse compounds. Rational ligand or drug design can provide directionality and help increase the possibility of success, even with a small library of compounds. In this article we have tried to give the reader an overview about sophisticated technologies and alternatives to peptides and nucleotides for protein purification and the art of ligand design for focused combinatorial synthesis.

Solar Panel Basics

Solar Panel Basics

Global warming is a huge problem which will significantly affect every country in the world. Many people all over the world are trying to do whatever they can to help combat the effects of global warming. One of the ways that people can fight global warming is to reduce their dependence on non-renewable energy sources like oil and petroleum based products.

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