Disclosed herein are botulinum neurotoxin (BoNT) polypeptides with a modified BoNT/B4 receptor binding domain (B4-HC) having amino acid mutations that modify the binding of the BoNT to the human SytII receptor. Specific mutations and combinations of mutations are disclosed. Isolated modified HCs, polypeptides comprising such modified HCs, chimeric molecules, pharmaceutical compositions, and methods of making and using the same are also disclosed. Methods of identifying additional such modified receptor binding domains, are further disclosed.
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机译:本文公开了具有修饰的BoNT / B4受体结合结构域(B4-H C Sub>)的肉毒杆菌神经毒素(BoNT)多肽,其具有改变BoNT与人SytII受体结合的氨基酸突变。公开了特定的突变和突变的组合。还公开了分离的修饰的HCs,包含该修饰的HCs的多肽,嵌合分子,药物组合物及其制备和使用方法。进一步公开了鉴定另外的这种修饰的受体结合结构域的方法。
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