Kesavan's Research Family

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Design and synthesis of novel privileged chiral ligands for asymmetric catalysis:

The development of efficient methods to provide enantiomerically enriched product is driven by the ever-increasing demand for non-racemic chiral chemicals. This is due to the often superior performance of the single enantiomer entities and/or because regulations demand the evaluation of both enantiomers of a biologically active compound before its approval. The ß-lactams are one of the best known and extensively investigated heterocyclic ring systems as a result of both their biological activity as antibiotics and their utility as synthetic intermediates. Among the different synthetic approaches for the preparation of ß-lactams, the Kinugasa reaction has been largely neglected in the current practice of organic chemistry. 

We dedicate our efforts in designing and synthesizing novel ligands from L-tartaric acid and their applications in several asymmetric transformations such as nitro aldol, Kinugasa and asymmetric hydrogenation reactions.

Design novel non-hydroxamate inhibitors against HDAC to treat cancer:

HDAC inhibitors so far reported mostly contain hydroxamic acid functionality that binds to a zinc in the active site including FDA approved vorinostat. They often present metabolic and pharmaco-kinetic problems such as glucoronidation and sulfation that result in a short in-vivo half-life. Upon hydrolysis, hydroxamates give hydroxylamine which has potential mutagenic properties.Because of such problems with the metabolic stability, toxicity and isozyme selectivity, it has become increasingly desirable to substitute hydroxamic acid functionality with another metal chelating group that possesses improved pharmaco-kinetic properties.

We therefore initiated a search for replacement group for hydroxamic acid with a goal of finding new tools for biological research. We have identified novel non-hydroxamate head group to bind with HDACs and synthesized them to test against cancer. We are currently doing screening of these compounds in various cancer cell lines.

Peptide mini-vectors for delivery of siRNAs:

It is widely anticipated that RNAi therapy will represent one of the key medical technologies of the future. However, a great deal of progress still needs to be achieved for this to be possible. In general terms, RNAi therapy may be defined as “the delivery of nucleic acids to patients for some therapeutic purpose”. Hence a major preoccupation of current RNAi research has been the design of appropriate vectors (viral and non-viral) for nucleic acid delivery. Here we propose an alternative, peptide-based system which represents one of the smallest and simplest vector systems for the delivery of siRNAs.

     Anticipated products and processes: