Compounds and methods relating to lysosomal storage disorders
AssigneesUniversity of Washington through its Center for Commercialization, PerkinElmer Health Sciences, Inc.
InventorsAlexander Cherkassky, Jason Cournoyer, Michael Gelb
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Abstract
Substrates are provided that include compounds suitable for detecting the activity of an enzyme such as a lysosomal storage enzyme where the substrates 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 methods for using substrates for detecting enzymatic activity using the inventive substrates.
Claims32
A substrate for analysis of an enzyme 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, 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;
- 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 C6-C20 heterocyclic containing a heteroatom of N, O or S.
A substrate for analysis of an enzyme comprising:
- 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;
- R1′ is a substituted or unsubstituted C, or N;
- R2′ is a substituted or unsubstituted C, a substituted or unsubstituted N, O, or S;
- R3′ is a substituted or unsubstituted C, N, or O;
- R4′ is a nullity, a substituted or unsubstituted C1-C2, O, or S;
- R1 is:
- a C1-C6 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;
- a C2-C7 alkenyl having a substituent of N, O, or S;
- R5′ is a nullity, a substituted or unsubstituted C1-C2;
- O, or S;
- and
- R6′ is 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;
- C6-C20 aryl;
- and C6-C20 heterocyclic containing a heteroatom of N, O or S.
The substrate of claim 13 wherein A is an aldohexose or ketohexose.
The substrate of claim 14 wherein A is a D-glucose or D-galactose.
A substrate for analysis of an enzyme comprising:
- where n is 0, 1, 2, 3, 4, or 5.
A molecule having formula:
- where 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, 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;
- 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 C6-C20 heterocyclic containing a heteroatom of N, O or S.
Dependencies are inferred from the claim text.