DNA-based Latest Drug Discovery Approaches

By Pharma Tech Outlook | Friday, March 15, 2019

In the past, the majority of the drugs were discovered either through the identification of the active ingredient from traditional remedies or through serendipitous finding. The drug discovery process involves identifying candidates, synthesizing, characterizing, screening, and testing for therapeutic effectiveness.

Affinity chromatography has been included in the list of most powerful and miscellaneous methods of chromatography used for the purification of a specific molecule or group of molecules. The technology has become increasingly important and useful in recent years. Weak Affinity Chromatography (WAC), an affinity-based liquid chromatographic technique used to separate chemical compounds to an immobilized target depending on their varied weak affinities.

DNA molecules are produced and transformed into a host organism in molecular cloning, where they are replicated. Molecular cloning is used to determine gene expression patterns and also to monitor expression changes in response to drug treatment.

The immobilized drug candidate incubates messenger RNA (mRNA) molecule libraries, and unbound protein-nucleic acid complexes are washed away. The complementary DNA (cDNA) is then amplified to create a library for proteins that bind the medication. DNA sequencing is used after subsequent selection to identify the cDNA. Protein microarrays are being developed as useful biopharmaceutical research tools. The differences in the characteristics of the individual proteins have made it difficult to develop compared to DNA sets. However, significant progress in the development of protein microarray technology has been made.

In reverse transfected cell microarrays also called live microarrays, live cells are used instead of proteins. The transfected cells express specific cDNAs at different locations in the array, meaning that the array is covered by cell clusters that over-express specific proteins in specific positions.

Biochemical suppression involves adding a small molecule to protein extracts that inhibits interest-inhibiting activity by means of an activity test. First, a protein extract is mixed with a molecule which inhibits the activity of interest. An uninhibited protein extract is then divided into the inhibited extract and determined whether any of the fractions suppresses the inhibition. When a fraction is identified which suppresses the inhibitory activity of the small molecule, further fractionation rounds are carried out to purify the suppressor activity. Thus the new scientific approaches have greatly enhanced knowledge or predictability of the number of drug targets and their responses to natural or synthetic ligands.

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