D-amino acid derivative-modified peptidoglycan and methods of use thereof

Patent metadata

Field	Value
Publication number	US-9303068-B2
Application number	US-201314092262-A
Country	US
Kind code	B2
Filing date	Nov 27, 2013
Priority date	Nov 30, 2012
Publication date	Apr 5, 2016
Grant date	Apr 5, 2016

Abstract

The present disclosure provides modified bacteria and modified peptidoglycan comprising modified D-amino acids; compositions comprising the modified bacteria or peptidoglycan; and methods of using the modified bacteria or peptidoglycan. The modified D-amino acids include a bioorthogonal functional group such as an azide, an alkyne or a norbornene group. Also provided are modified peptidoglycans conjugated to a molecule of interest via a linker.

First claim

What is claimed is:

1. An isolated, modified peptidoglycan (PG) comprising at least one modified D-amino acid chemically conjugated to a reagent via a heterocycle, wherein the modified D-amino acid is an azide-modified, an alkyne-modified, or a norbornene-modifed D-amino acid, and the reagent is an azide-containing reagent, an alkynyl reagent or a norbornene-reactive reagent.

2. The isolated, modified PG of claim 1 , wherein the reagent comprises a detectable label.

3. The isolated, modified PG of claim 1 , wherein the reagent comprises a therapeutic agent.

4. The isolated, modified PG of claim 1 , wherein the reagent comprises an immunomodulatory molecule.

5. A composition comprising:
a) an isolated, modified peptidoglycan comprising at least one modified D-amino acid, wherein the modified D-amino acid is chemically conjugated to a reagent selected from an azide-containing reagent, an alkynyl reagent and a norbornene-reactive reagent, and the isolated, modified peptidoglycan is described by the formula:
PG-L 1 -Z-L 2 -Y

wherein:
PG is the modified peptidoglycan, L 1 and L 2 are independently optional linkers, Z is a heterocycle, and
Y is a therapeutic agent or an immunomodulatory molecule; and
b) a pharmaceutically acceptable excipient.

6. The composition of claim 5 , wherein Y is a therapeutic agent.

7. The composition of claim 5 , wherein Y is an immunomodulatory molecule.

8. The composition of claim 7 , wherein Y is an antigen.

9. The isolated, modified PG of claim 1 , wherein the modified D-amino acid is an azide-modified D-amino acid, and the reagent is an alkynyl or phosphine reagent.

10. The isolated, modified PG of claim 1 , wherein the modified D-amino acid is an alkyne-modified D-amino acid, and the reagent is an azide or alkynyl reagent.

11. The isolated, modified PG of claim 1 , wherein the modified D-amino acid is a norbornene-modified D-amino acid, and the reagent is a norbornene-reactive agent.

12. The isolated, modified PG of claim 2 , wherein the detectable label is a fluorophore.

13. The isolated, modified PG of claim 2 , wherein the detectable label is a radioactive isotope.

14. The isolated, modified PG of claim 2 , wherein the detectable label is biotin.

15. The isolated, modified PG of claim 2 , wherein the detectable label is a peptide that can be detected by antibody binding.

Assignees

• Univ California

Inventors

• Bertozzi Carolyn R
• Sloan Siegrist Palmore Mary
• Jewett John C
• Gordon Chelsea G
• Shieh Peyton

Classifications

• C07K9/001

  the peptide sequence having less than 12 amino acids and not being part of a ring structure · CPC title

• C07K14/195

  from bacteria · CPC title

• C12Q1/18

  Testing for antimicrobial activity of a material · CPC title

• C07K9/00 Primary

  Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof · CPC title

• C07K14/4725

  Proteoglycans, e.g. aggreccan · CPC title