Development of enabling technologies for translating bioactive peptides into therapeutics
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Protein-protein interactions play a key role in vital cell functions. Modulating these interactions is an emerging paradigm for drug discovery. It has proven to be a daunting task for small, drug-like molecules to effectively inhibit protein-protein interactions. Since helices play a major role in mediating these interactions, there has been a significant advance in the last decade in designing peptide based ligands that mimic helical protein interfaces to inhibit protein-protein interactions. Though peptides can be ideal candidates; but, their poor cell permeability and proteolytic stability limits their potential as drug candidates. Hence, we developed various strategies to overcome the limitations of peptide drugs. These include: 1) stabilization of peptide helices through side-chain cross-linking via a) 1, 3-dipolar cycloaddition and b) cysteine based alkylation chemistries and 2) conjugation of peptide to a carrier protein in an attempt to achieve selective delivery.