Improving the therapeutic index is a major impetus for innovation in many therapeutic areas such as cancer, inflammatory and other infectious diseases. Today the vast majority of clinically used drugs exhibit very short half life in the blood stream and high overall clearance rate. Target specific drug delivery systems have the potential to revolutionize the treatment and diagnosis of many diseases like cancer and other infectious diseases. We are trying to develop novel multifunctional biodegradable nanocarrier that deliver drug specifically to the tumors. Drug molecule was incorporated to the vehicle via a peptide linker that enables the release of the drug by the lysosomal enzyme Cathepsin. Small peptide based ligands will be utilized to target EGFR and VEGFR. Target specificity, enhanced potency, and prolonged delivery of the drug at the site of action compared the traditional chemotherapeutic agents may result a novel Nano Drug Delivery System (NDDS).

The discovery that certain chemokine receptors could function as co receptors for HIV entry has opened a new arena in the field of anti-HIV treatment.The natural chemokine ligands of these receptors can compete with HIV for binding to these receptors thereby playing a major role in inhibiting HIV entry. But their use on a therapeutic scale has been hampered by the lack of receptor selectivity and proinflammatory properties. In this study we use CXCR4 and CCR5 chemokine receptors and their ligands as model systems to develop chemokine analogues which can block the cellular entry of HIV-1 with reduced toxicity and side effects. Fmoc solid phase peptide synthesis was used for the synthesis of analogues.

Over the past decade, level of bacterial resistance to antibiotics has risen dramatically and became a real threat to public health. Thus there is a growing need to discover and develop new drugs. The amphibians especially the frog skin is found to be an excellent source of anti microbial peptides which are considered as one of the potent candidate for new target antibiotics. These peptides participate in the innate immune response by providing a rapid first line defense. My work primarily involves the isolation of novel peptides from frog Rana curtipes skin secretion, screening their activity against various bacterial and fungal strains. The structure function studies of these peptides will also be carried out to gain insight into their mechanism of action.

My work involves the structure-function studies of the antimicrobial peptides. These peptides are isolated by transcriptomic and peptidomic approaches from the skin secretion of frog Hylarana temporalis, endemic to Western Ghats. Multinucleated cells of amphibian skin synthesize a wide range of bioactive molecules with potential for the development of pharmaceutical agents. Amino acid sequencing and MALDI TOF TOF techniques were used to find out the sequential arrangement of amino acids in the peptide. These peptides and several of their analogous were chemically synthesized to establish their mechanism of action and structure activity relations which may lead to the development of AMPs as a new class of drug with very high therapeutic index.

Chemical ligation is the chemoselective reaction of the two peptide segments in water at pH 7 is an alternative chemical technique to make proteins and their analogous. My work involves the development of new polymer support for the synthesis of modified proteins with D-amino acids, N-methyl amino acids, ?-amino acids etc by chemical ligation technique which otherwise is not possible by the recDNA technology. One peptide segment is the peptide thioester which can be cleaved from the support only upto 40% under optimum reaction conditions. I am trying to increase peptide–?-thioester cleavage yield to above 80% from the existing 40% by using a new PEG polymer with a modified liker under a set of condition. Temperature, pH and thiol additives for nucleophilic displacement are some of the important parameters that influence the cleavage. This technique will be used to synthesize proteins and their analogous.

Efficacy of antibacterial peptides as novel therapeutic agents is hampered by their poor in vivo half-life, rapid renal filtration, proteolytic degradation, and increased intracellular uptake by the reticuloendothelial system. Since most of these peptides are isolated from nonhuman sources they may elicit strong immune response. Repeated administration therefore may result the drug neutralization and rapid clearance by the antibodies. I am investigating the effect of PEGylation, palmitoylation etc on antimicrobial activity, stability, and clearance from the body. Ability of these derivatives to escape the proteolytic enzymes and uptake by dendritic cells and antigen processing were also very interesting. These peptides and their derivatives were chemically synthesized on a polymeric support developed by crosslinking a tetra functional 3,3´ (PEG200)bis (1-(4-vinylphenoxy) propan-2-ol) with polystyrene {PS-bis(VPP)PEG200}. In this resin functional groups are confined only to the surface of the resin bead. This helps the incorporation of higher molecular mass PEGs and other higher fatty acids with very high efficiency.