Variant, Recombinant Beta-Glucocerebrosidase Proteins With Increased Stability And Increased Retained Catalytic Activity

摘要

Described herein are variant, recombinant β-glucocerebrosidase proteins characterized as having increased stability relative to recombinant wild-type β-glucocerebrosidase. Also provided herein are variant, recombinant β-glucocerebrosidase proteins characterized as retaining more catalytic activity relative to recombinant wild-type β-glucocerebrosidase. Further described herein are variant, recombinant β-glucocerebrosidase proteins that can have amino acid variations at one or more of the following positions: 316, 317, 321 and 145. Methods of making the variant, recombinant β-glucocerebrosidase proteins are also described as well as methods of treating patients having lysosomal storage diseases.

主权项

1. A variant, recombinant human β-glucocerebrosidase protein, wherein the protein has at least one of the following substitutions relative to SEQ ID NO: 1: F316A, L317F, K321V, K321A, H145L and H145F.