Disclosed herein are modified Clostridial Botulinum neurotoxin (BoNT) polypeptides with a modified receptor binding domain of Clostridial Botulinum serotype B, comprising one or more substitution mutations at positions corresponding 1248 or 1249 in serotype B, strain 1. Specific substitution mutations include I1248F, I1248Y, I1248H, I1248W, V1249W, V1249F, V1249Y, V1249H, I1248W/V1249F, I1248W/V1249Y, I1248W/V1249H, I1248F/V1249Y, I1248F/V1249H, I1248Y/V1249H, I1248F/V1249W, I1248Y/V1249W, I1248H/V1249W, I1248Y/V1249F, I1248H/V1249F, or I1248H/V1249Y. Other substitution mutations are also disclosed. Isolated modified receptor binding domains, chimeric molecules, pharmaceutical compositions, and methods of using the same are also disclosed.Se describen polipeptidos modificados de la neurotoxina Clostridial Botulinum (BoNT) con un dominio de union al receptor modificado del serotipo B (BoNT/B) Clostridial Botulinum, que comprende una o mas mutaciones de sustitucion en las posiciones correspondientes a 1248 o 1249 en el serotipo B, cepa 1； las mutaciones de sustitucion especifica incluyen I1248F, I1248Y, I1248H, I1248W, V1249W, V1249F, V1249Y, V1249H, I1248W/V1249F, I1248W/V1249Y, I1248W/V1249H, I1248F/V1249Y, I1248F/V1249H, I1248Y/V1249H, I1248F/V1249W, I1248Y/V1249W, I1248H/V1249W, I1248Y/V1249F, I1248H/V1249F, o I1248H/V1249Y； tambien se describen otras mutaciones de sustitucion； tambien se describen los dominios de union al receptor modificado aislado, las moleculas quimericas, las composiciones farmaceuticas y los metodos de uso de las mismas.
