Stabilized peptoid-peptide hybrids and uses thereof

Patent metadata

Field	Value
Publication number	US-10197575-B2
Application number	US-201515300451-A
Country	US
Kind code	B2
Filing date	Mar 31, 2015
Priority date	Mar 31, 2014
Publication date	Feb 5, 2019
Grant date	Feb 5, 2019

Abstract

The current invention pertains to stabilized peptoids or peptoid-peptide hybrids. The peptoids or peptoid-peptide hybrids are stabilized by side chain-side to side chain linkages and/or backbone cyclization. The current invention also provides a positional library scanning method for identification of peptoids or peptoid-peptide hybrids having a desired biological activity.

First claim

We claim:

1. A stapled peptoid comprising a plurality of N-substituted glycines, wherein at least two of the N-substituted glycines are linked to each other by an intramolecular cross-link between the N-substitutions, and wherein the length and geometry of the cross-link pre-organizes the peptoid into a desired conformation.

2. A stapled peptoid-peptide hybrid comprising a plurality of amino acids and a plurality of N-substituted glycines, wherein at least two residues from the plurality of amino acids and the plurality of N-substituted glycines are linked to each other by an intramolecular cross-link, and wherein the length and geometry of the intramolecular cross-link provides stability to the peptoid-peptide hybrid.

3. The stapled peptoid-peptide hybrid of claim 2 , wherein two N-substituted glycine residues or two amino acid residues are linked to each other by the intramolecular cross-link.

4. The stapled peptoid-peptide hybrid of claim 2 , wherein an N-substituted glycine residue is linked to an amino acid residue by the intramolecular cross-link.

5. The stapled peptoid-peptide hybrid of claim 2 , wherein the peptoid-peptide hybrid is a cyclic peptoid-peptide hybrid, the cyclic peptoid-peptide hybrid comprising a plurality of alternating peptoid-peptide sequences, wherein the peptoid-peptide sequences form at least two antiparallel beta-strands.

6. The stapled peptoid-peptide hybrid of claim 2 , further comprising substitutions on the amino acid side chains or the N-substitutions on glycines, wherein the substitutions further stabilize the peptoid-peptide hybrids.

7. The stapled peptoid-peptide hybrid of claim 2 , wherein one or more of the substitutions are selected from the groups listed in Table 1 or shown in FIG. 9 , and wherein the substitutions may be the same or different.

8. The stapled peptoid-peptide hybrid of claim 2 , wherein the peptoid-peptide hybrid is selected from formula I, formula II, formula III, formula IV, formula V, formula VI, formula VII, formula VIII, formula IX, formula X, formula XI, or formula XII.

9. The stapled peptoid-peptide hybrid of claim 8 , wherein one or more of the R groups are selected from the groups listed in Table 1 or shown in FIG. 9 .

10. The stapled peptoid-peptide hybrid of claim 2 , wherein the peptoid-peptide hybrid is that of FIG. 1A , optionally including the attached linker, or optionally including the attached linker and resin.

11. The stapled peptoid-peptide hybrid of claim 10 , wherein one or more of the R groups (R 1 , R 2 , R 3 , or R 4 ) are selected from the groups listed in Table 1 or shown in FIG. 9 .

12. The stapled peptoid-peptide hybrid of claim 2 , wherein the peptoid-peptide hybrid is that of FIG. 1B or 1C .

13. The stapled peptoid-peptide hybrid of claim 2 , wherein the peptoid-peptide hybrid is that of FIG. 3 , FIG. 4 , FIG. 5 , or FIG. 6 .

14. The stapled peptoid-peptide hybrid of claim 13 , wherein one or more of the variable side chains are selected from the groups listed in Table 1 or shown in FIG. 9 .

15. The stapled peptoid-peptide hybrid of claim 2 , wherein the peptoid-peptide hybrid is that of FIG. 7 or FIG. 8 , optionally including the attached resin.

16. A positional library of the peptoid-peptide hybrid of claim 2 .

Assignees

• H Lee Moffitt Cancer Ct & Res
• Univ South Florida

Inventors

• Mclaughlin Mark
• Sarnaik Amod A

Classifications

• C07K14/00 Primary

  Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof · CPC title

• C07K7/64 Primary

  Cyclic peptides containing only normal peptide links · CPC title

• G01N33/6845 Primary

  Methods of identifying protein-protein interactions in protein mixtures · CPC title

• G01N33/68

  involving proteins, peptides or amino acids {(involving lipoproteins G01N33/92)} · CPC title

• G01N33/6842

  Proteomic analysis of subsets of protein mixtures with reduced complexity, e.g. membrane proteins, phosphoproteins, organelle proteins · CPC title