Tethering cysteine residues using cyclic disulfides
AssigneeBrandeis University
InventorsJeffrey N. Agar, Joseph Salisbury
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Abstract
Described herein are compounds and methods for tethering proteins. For example, dimers of proteins, including SOD1 and DJ-1, are described, where the dimers are formed by the covalent bonding of a cysteine on the first monomer to a cysteine on the second monomer via a cyclic disulfide linker. The covalently attached dimers exhibit increased stabilization.
Claims18
A method of treating a subject suffering from Amyotrophic Lateral Sclerosis (ALS), Parkinson's disease, or Alzheimer's disease, comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of Formula I, wherein
- the compound of Formula I is
- wherein
- Y is S, S═O, or S(═O)2;
- n is 0, 1, 2, 3, or 4;
- and
- R is independently selected from the group consisting of —H, —OH, —NH2, —NHR′, —N(R′)2, alkyl, —OMs, —OTs, —OTf, and —CO2H;
- or any two geminal R groups, taken together, form an imine;
- or any two vicinal R groups, taken together, form a ring;
- wherein any alkyl or imine may be substituted with a carbamide, a carboxylate, or a hydroxyl.
A method of treating a subject suffering from Amyotrophic Lateral Sclerosis (ALS), Parkinson's disease, or Alzheimer's disease, comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of Formula II, wherein the compound of Formula II is
- wherein
- R″ is-H, alkyl, or aryl, or both R″, taken together, form a ring;
- wherein any alkyl, aryl, or ring may be substituted with-OH, alkyl, or halo.
Dependencies are inferred from the claim text.