Inhibitors of RGS proteins
View Patent ↗The present invention relates to novel inhibitors of G-protein signaling. In particular, the present invention provides peptide inhibitors of G protein signaling proteins and methods of using such inhibitors to modulate physiological effects of G protein signaling. The present invention thus provides novel drug targets for a variety of pathologies mediated by defects in G-protein signaling.
1. A constrained peptide, wherein said constrained peptide is selected from the group consisting of:
a is an amino acid with an amine side chain, b is an amino acid with a carboxyl side chain, and q is 1 and r is an integer between 0 and 10, and wherein Xn is V-K or Ac-V-K; wherein Zp is E; and wherein Ym is selected from the group consisting of: T-G-I, T-Hfe-I, T-G-F, T-(D-Ser)-I, and T-G-Y.
2. A constrained peptide, wherein said constrained peptide is selected from the group consisting of:
3. The constrained peptide of claim 1 , wherein Xn comprises V-K.
4. The constrained peptide of claim 1 , wherein Xn comprises Ac-V-K.
5. The constrained peptide of claim 1 , wherein a is 1,4 diamino butanoic acid.
6. The constrained peptide of claim 1 , wherein a is ornithine.
7. The constrained peptide of claim 1 , wherein a is lysine.
8. The constrained peptide of claim 1 , wherein b is glutamate.
9. The constrained peptide of claim 1 , wherein Ym is T-G-I.
10. The constrained peptide of claim 1 , wherein Ym is T-Hfe-I.
11. The constrained peptide of claim 1 , wherein Ym is T-G-F.
12. The constrained peptide of claim 1 , wherein Ym is T-(D-Ser)-I.
13. The constrained peptide of claim 1 , wherein Ym is T-G-Y.