COMPOUNDS AND METHODS RELATING TO LYSOSOMAL STORAGE DISORDERS

摘要

Methods are provided for detecting enzymatic activity of various lysosomal storage enzymes using substrates that include: a sugar moiety; a linker moiety allowing the conjugation of sugar moiety with the remaining structure of the substrate; and two or more fatty acid chains or derivatives thereof at least one of which is sufficiently structured to provide improved solubility in aqueous or organic solvent systems. Also provided are internal standards, and inhibitors for use in detecting or reducing enzymatic activity using the inventive substrates.

主权项

1. A method for detecting enzymatic activity, comprising:
contacting a sample containing a target enzyme with a substrate, under conditions wherein the target enzyme is capable of acting on the substrate to produce an enzymatic product; and detecting said enzymatic product; the substrate having formula: where A is a monosaccharide or a disaccharide linked to O by a glycosidic bond; B1 is selected from the group consisting of: a C1-C20 alkyl; a heteroatom containing C1-C20 alkyl; C2-C20 alkenyl; a heteroatom containing C2-C20 alkenyl; and a substituted or unsubstituted C6-C20 aryl; B2 is selected from the group consisting of: a C2-C7 urethane; a C2-C7 amido; a C2-C7 ester; a C2-C7 uriedo; a C2-C7 carbamato; a C2-C7 carbonyl; a C1-C7 alkyl; a heteroatom containing C1-C7 alkyl; a C1-C7 alkyl having a substituent of N, O, or S; a C2-C7 alkenyl; a heteroatom containing C2-C7 alkenyl; and a C2-C7 alkenyl having a substituent of N, O, or S; and B3 is selected from the group consisting of: a C1-C20 alkyl; a heteroatom containing C1-C20 alkyl; C1-C20 alkyl having a substituent of N, O, or S; C4-C20 ether; C1-C20 ester, C1-C20 alkenyl; a heteroatom containing C1-C20 alkenyl; C2-C20 alkenyl having a substituent of N, O, or S; C1-C20 alkynl; a heteroatom containing C1-C20 alkynl; C2-C20 alkynl having a substituent of N, O, or S; C6-C20 aryl; and a C6-C20 heterocyclic containing a heteroatom of N, O or S.