Engineered botulinum neurotoxin

摘要

Disclosed herein are botulinum neurotoxin (BoNT) polypeptides with a modified receptor binding domain of Clostridial botulinum serotype B (B-Hc), comprising one or more substitution mutations corresponding to substitution mutations in serotype B, strain 1, V1118M; Y1183M; E1191M; E1191I; E1191Q; E1191T; S1199Y; S1199F; S1199L; SI 20 IV; or combinations thereof. Specific combination mutations include E1 191M and S1199L, E1191M and S1199Y, E1191M and S1199F, E1191Q and S1199L, E1191Q and S 1199Y, or E 1191 Q and S 1199F. Other substitution mutations are also disclosed. Isolated modified receptor binding domains, chimeric molecules, pharmaceutical compositions, and methods of using the same are also disclosed.

主权项

1. A polypeptide comprising a modified receptor binding domain of Clostridial botulinum serotype B (B-Hc) comprising an amino acid substitution mutation at the amino acid position E1191 of the polypeptide of SEQ ID NO: 4 with M, Q, C, V, Y, T or I, wherein the substitution mutation produces enhanced binding of the modified B-Hc to human SytII as compared to an identical molecule lacking the substitution mutation.