Application of molecular biology knowledge in developing new

drugs
Molecular biology plays an important part in development of new drugs. Molecular biology
knowledge is applied during different stages of a drug development like in identifying new
drug targets , developing a suitable drug capable of acting on target and also to analyse the
safety of the drug. Molecular biology knowledge is also applied for gene therapies like in the
treatment of parkinsons . In parkinsons patients the overactive nerve cells in the basal
ganglia are controlled by GABA which is produced by the gene introduced through gene
therapy . It has been speculated that in future molecular biology will play a bigger role in
developing therapies.

Molecular networks
Most of the major human diseases like diabetes, certain types of cancer ,are very complex.
These diseases are a result of interaction between many genes and environmental factors.
These complicated molecular networks are studied through computation and experiments to
understand them better. For the development of new drugs nowadays molecular networks
have to be intensively studied. Information about many molecular networks are now available
in certain databases where they are represented in graphs with nodes and vertices indicating
the biological molecules , their interaction and links to other molecules. For generating these
graphs information on gene regulation and protein- protein interaction are usually collected.

Fig 1-This figure illustrates the baisc concepts of molecular networks. Large number of
interactions can be described as hub , while proteins that connects sub networks are called as
bottlenecks

These molecular networks are useful in identifying drug targets when the three dimentional
structure of the target is not known. These networks are also useful in finding new therapies
for existing drugs. This repositioning of drugs is eliminates the lengthy process of identifying
a new drug.

Molecular toxicology
This field involves application of molecular biology techniques for assessing the safety and
toxicity of the drugs. the various molecular biology techniques used in molecular toxicology
includes metabolomics, transcription profiling, gene expression, cDNA library screening, etc
to identify the changes in mRNA or the final protein in response to certain conditions.
Various mechanisms of toxicity exists in human body that carry different levels of risk. One
way to determine whether these toxicity mechanisms occur in response to a drug at different
environments is to perform microarrays, boutique arrays with toxicologically relevant genes
during early invivo studies. Knowledge about a specific toxicity mechanism can be obtained
using techniques like transcription profiling, metabolomics studies and other molecular
techniques described above. The main mechanisms related to toxicity and are clinically
relevant are apoptosis and proliferation, phospholipidoses, mitochondrial toxicity. The
knowledge about mechanisms were obtained with the help of molecular biology techniques.

Examples for application of molecular biology in developing

drugs
1)Developing drugs using toxins
Certain toxins are modified and used in treatment of certain diseases using molecular biology
techniques . An example of it is the drug used to treat autoimmune diseases developed from
the toxin shK from sun anemone (Stichodactyla helianthus) . This toxin is capable of
inhibiting a potassium channel Kv1.3 of T lymphocyte activity was found to be increased in
humans containing autoimmune diseases. But the problem with directly using this toxin is
that it also inhibits Kv1.1 potassium channel present in the neurons. Hence various forms of
toxin were produced using molecular biology techniques to identify the form that that was
capable of inhibiting only the Kv1.3 channel in the T lymphocyte. Finally they identified the
form that contained an additional amino acid in the N-terminus that was capable of blocking
only the channels present in the T lymphocyte. Later it was found that this drug was also

capable of reversing paralysis in rodent models affected with multiple sclerosis. This drug is
yet to be approved by the FDA .
Another drug that was developed from a toxin and has been approved by the FDA is the one
that is chemically similar to a toxin found in cone snail is the painkiller prailt. When this is
injected into the spine the pain signals to the brain is blocked by this prailt drug which acts by
blocking the calcium ion channels.
Another painkiller containing a peptide similar to a toxin found from black mamba is also
under approval for commercial sale. These peptides has the capacity to inhibit acid sensing
ion channels. In mice models they proved to be more potent than morphine and didnt exhibit
any toxicity.

Development of anti TB drugs

According to WHO survey 2 million deaths occur each year due to TB. The current
chemotherapy treatment used to treat TB involves first administering first line drugs which is
a cocktail of six drugs for 6 months. If this fails than second line drugs are given which
exhibits certain level of toxicity. The presence of dormant bacteria in the lesions makes the
treatment more difficult. These first and second line drugs target only a few metabolic
processes like cell wall synthesis, DNA synthesis. Currently scientists are trying to find a new
drug target that doesnt allow the bacteria to persist silently. Sequencing of the complete
genome of the TB bacteria has led to the discovery of new targets. Nitroimidazoxacines
(PA824) is currently under clinical trial phase 2. This drug inhibits the synthesis cell wall
lipids and protein of TB bacteria even in dormant bacteria. The cell wall of the M.
tuberculosis is very important for the survival of those bacteria inside the cell of the host.
This drug reduces the aromatic nitrogen groups to intermediate nitrogen radical.
The derived oxazoles are also suitable candidates for treatment of TB . The drug OPC-67683,
also under trail, is also a derived oxazales. It is active against both active and dormant strains.
It has long half life. It inhibits the synthesis of keto-mycolic and methoxy-mycolic acid.

Conclusion
As seen from the above examples molecular biology is an effective tool in the development
of drug. The important role that molecular biology plays in developing drug has been realised
only during the past few decades. With the molecular biology knowledge currently available
developing drugs has become a possibility for many diseases that were initially thought to be
incurable. In future the role that molecular biology will play even bigger role in drug
development .

References
1) Khasnobis, S., et al . Emerging therapeutic targets in tuberculosis: post-genomic era.
Expert Opinion on Therapeutic Targets, Vol. 6,.1.2002:21-40
2)
3) Bocanegra-Garca4 et al. Antitubercular drugs development.recent advances in
therapeutic drugs. Vol7.2011. ;207-242.
Text book
1)Riccado et al . computational drug design and development. Vol819. 2012.628pgs.