Publications by authors named "Candice R Warner"

Article Synopsis
  • The study focuses on creating peptide-based ligands using a method called protein catalyzed capture (PCC) to improve molecular binders for sensing and drug delivery.
  • Two specific peptides were enhanced: one targeting vascular endothelial growth factor (VEGF) for imaging in living organisms, showing stability and a suitable half-life, and another targeting the protective antigen (PA) of Bacillus anthracis for use in challenging conditions without losing function.
  • The research highlights the effectiveness of the PCC screening process in developing advanced alternatives to traditional antibodies for diagnostics and therapeutics.
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We constructed a genetic fusion of a single domain antibody (sdAb) with the thermal stable maltose binding protein from the thermophile Pyrococcus furiosus (PfuMBP). Produced in the Escherichia coli cytoplasm with high yield, it proved to be a rugged and effective immunoreagent. The sdAb-A5 binds BclA, a Bacillus anthracis spore protein, with high affinity (K(D) ∼ 50 pM).

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Mutation of surface residues to charged amino acids increases resistance to aggregation and can enable reversible unfolding. We have developed a protocol using the Rosetta computational design package that "supercharges" proteins while considering the energetic implications of each mutation. Using a homology model, a single-chain variable fragment antibody was designed that has a markedly enhanced resistance to thermal inactivation and displays an unanticipated ≈30-fold improvement in affinity.

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