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