Farrow, Blake published the artcileEpitope Targeting of Tertiary Protein Structure Enables Target-Guided Synthesis of a Potent In-Cell Inhibitor of Botulinum Neurotoxin, COA of Formula: C28H37NO9, the main research area is tertiary protein target guided indium cell inhibitor botulinum neurotoxin; botulinum neurotoxin; combinatorial screening; epitope targeting; peptides; target-guided synthesis.
Botulinum neurotoxin (BoNT) serotype A is the most lethal known toxin and has an occluded structure, which prevents direct inhibition of its active site before it enters the cytosol. Target-guided synthesis by in situ click chem. is combined with synthetic epitope targeting to exploit the tertiary structure of the BoNT protein as a landscape for assembling a competitive inhibitor. A substrate-mimicking peptide macrocycle is used as a direct inhibitor of BoNT. An epitope-targeting in situ click screen is utilized to identify a second peptide macrocycle ligand that binds to an epitope that, in the folded BoNT structure, is active-site-adjacent. A second in situ click screen identifies a mol. bridge between the two macrocycles. The resulting divalent inhibitor exhibits an in vitro inhibition constant of 165 pM against the BoNT/A catalytic chain. The inhibitor is carried into cells by the intact holotoxin, and demonstrates protection and rescue of BoNT intoxication in a human neuron model.
Angewandte Chemie, International Edition published new progress about Cytosol. 882847-32-7 belongs to class esters-buliding-blocks, name is 1-(9H-Fluoren-9-yl)-3-oxo-2,7,10,13,16,19-hexaoxa-4-azadocosan-22-oic acid, and the molecular formula is C28H37NO9, COA of Formula: C28H37NO9.
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