Design of Artificial Glycosidases: Metallopeptides that Remove H Antigen from Human Erythrocytes

摘要

Catalysts that promote carbohydrate degradation have a wide range of potential applications, but the use of either enzyme glycosidases or small-molecule catalysts in biological systems raises significant challenges. Herein, we demonstrate a novel strategy for the design of synthetic agents that mimic natural glycosidases and address current problems for biological use. This strategy is illustrated by application to the development of potential blood substitutes for the rare Bombay blood type that is characterized by a deficiency of H2 antigen. Metallopeptides with 16 to 20 amino acids were constructed as artificial fucosidases that exhibit selective carbohydrate cleavage reactivity toward L-fucose over d-glucose. Selective fucose cleavage from the H2-antigen saccharide enables efficient removal of H2 antigen from erythrocytes and thereby accomplishes the conversion of regular human type-O blood into a potential blood substitute for the rare Bombay blood type.