Compositions and methods for treating mitochondrial neurogastrointestinal encephalopathy
AssigneeEntrada Therapeutics, Inc.
InventorsNatarajan Sethuraman, Jason Ruth, Louis A. Tartaglia, Dehua Pei, Ziqing Qian
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Abstract
Disclosed herein are compositions and methods of treating disclosure provides for compounds for use in treating Mitochondrial Neurogastrointestinal Encephalopathy Syndrome (MNGIE). In some embodiments, the compounds have cell penetrating activity and thymidine phosphorylase activity. In certain embodiments, the compounds disclosed herein comprise: a) at least one cell-penetrating peptide (CPP) moiety; and b) a thymidine phosphorylase, or an active fragment or analog thereof (TP), wherein the CPP is coupled, directly or indirectly, to TP.
Claims18
A compound having a stricture according to Formula I-A:
- CPP-L-TP (I-A),
- wherein:
- CPP is a cyclic cell-penetrating peptide (cCPP);
- TP is thymidine phosphorylase, or an active fragment or analog thereof;
- and has an amino acid sequence that is at least 95% identical to SEQ ID NO. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or 13;
- L is a linker;
- and
- wherein L is a covalently bound to the side chain of an amino acid on the CPP and to the N-terminus of the TP;
- the cCPP has a sequence comprising any of Formula IV-A-D:
- wherein:
- each of AAH1 and AAH2 are independently a D or L hydrophobic aromatic amino acid;
- at each instance and when present, each of AAU and AAZ are independently a D or L amino acid;
- m and n are independently selected from a number from 0 to 6;
- and
- wherein Formula IV-A-D comprise at least three consecutive arginine, and at least three-consecutive hydrophobic aromatic amino acids.
Dependencies are inferred from the claim text.