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Damodara Reddy N, Ph.D.

Sr Scientist,Division Of Medicinal and Process Chemistry

Molecular Editing, Late Stage Modification and Bio-Conjugation of Therapeutic Peptides,
Natural Products and Approved Drugs

One of the major research work in our lab focus on molecular editing, late stage modification and drug delivery of therapeutic peptides and small molecules. Therapeutic peptides offer several advantages over traditional organic drugs, they offer greater efficacy, selectivity and specificity and the metabolized products minimizing the risks of side effects. However, the lack of oral bioavailability is certain limitation of most peptides. To overcome these problems, we do the site selective modifications of peptides, proteins and complex natural products. Our group also works on cutting edge of medicinal chemistry, biocompatable nanomaterials synthesis and their applications in drug delivery.

1. Molecular Editing

Molecular editing is an advance concept to improve the bioavailability of drugs, where we replace one atom with a hetero atom or functional group in an orally available drugs or molecules in the advanced stage. Using this concept, we modify the therapeutic peptides and bioactive small molecules in site-selective manner by using various methodologies as shown in below diagram.

2. Late-stage modification,

The concept late-stage functionalization (LSF) involves selective functionalization of the C–H/N-H bonds in the presence of many other functional groups in a peptide or in a bioactive scaffold. This allows chemists to generate chemical libraries of lead compound and natural products analogues. Site selectively decorated peptides bears great potential for drug discovery, proteomics and diagnostics. In our laboratory, we develop various methodologies including metal catalysis and metal free condition for the post-translational modification of therapeutic peptides, natural products and approved drugs.

3. Staple peptides and their Biomedical applications:

The peptide secondary structure represents a common structural motif that targets protein-protein and protein-DNA interactions. The short peptides can lose their secondary structure when taken out of context, developing chemical interventions to stabilize their bioactive structure remains an active area of research. Stapled peptides are new class of compounds have been developed by various methods to mimic α-helix secondary structures and are being used to understand the important biological mechanisms. Our group developed novel staple peptides and we study their ligand/protein interactions, metabolic stability, lipid membrane interactions and cell permeability to identifying bioavailability. We conjugate these peptides with florescent and drug molecules, which could be used in various biomedical applications as represented in below figure.