Computational and Biomolecular NMR Guided Design of Peptide Theraputics for Influenza A
2014
Peptidomimetic drugs are a rapidly growing field for treatment of disease. With the current screening-based approach yielding fewer and fewer drug candidates, peptide drugs appear to be the next frontier of disease treatment. Still, the issues of structural stability and half-life exist for peptides due to the vast number of proteases in the cell. We combine computational structure-guided design and solution NMR techniques including 19F NMR to rapidly design and screen peptide inhibitors for both protein:protein interactions (PPI) and protein:nucleotide interactions (PNI). Structural stability is greatly increased by utilizing D-amino acids at alpha helix termini, which also may enhance metabolic half-life. Both PPI and PNI interfering peptides demonstrate promising binding activity to target sites.
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