Matches in SemOpenAlex for { <https://semopenalex.org/work/W2910366127> ?p ?o ?g. }
- W2910366127 abstract "Although botulinum neurotoxin serotype A (BoNT/A) products are common treatments for various disorders, there is only one commercial BoNT/B product, whose low potency, likely stemming from low affinity toward its human receptor synaptotagmin 2 (hSyt2), has limited its therapeutic usefulness. We express and characterize two full-length recombinant BoNT/B1 proteins containing designed mutations E1191M/S1199Y (rBoNT/B1MY) and E1191Q/S1199W (rBoNT/B1QW) that enhance binding to hSyt2. In preclinical models including human-induced pluripotent stem cell neurons and a humanized transgenic mouse, this increased hSyt2 affinity results in high potency, comparable to that of BoNT/A. Last, we solve the cocrystal structure of rBoNT/B1MY in complex with peptides of hSyt2 and its homolog hSyt1. We demonstrate that neuronal surface receptor binding limits the clinical efficacy of unmodified BoNT/B and that modified BoNT/B proteins have promising clinical potential." @default.
- W2910366127 created "2019-01-25" @default.
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- W2910366127 date "2019-01-04" @default.
- W2910366127 modified "2023-10-06" @default.
- W2910366127 title "Engineered botulinum neurotoxin B with improved binding to human receptors has enhanced efficacy in preclinical models" @default.
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- W2910366127 doi "https://doi.org/10.1126/sciadv.aau7196" @default.
- W2910366127 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6357751" @default.
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- W2910366127 hasPublicationYear "2019" @default.
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