D-amino acid derivative-modified peptidoglycan and methods of use thereof
AssigneeThe Regents of the University of California
InventorsCarolyn R. Bertozzi, Mary Sloan Siegrist Palmore, John C. Jewett, Chelsea G. Gordon, Peyton Shieh
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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.
Claims16
An isolated, modified peptidoglycan comprising at least one modified D-amino acid comprising a bioorthogonal group.
An isolated, modified peptidoglycan 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-modified D-amino acid, and the reagent is an azide-containing reagent, an alkynyl reagent or a norbornene-reactive reagent.
A modified bacterial cell comprising a modified peptidoglycan, wherein the modified peptidoglycan comprises at least one modified D-amino acid, wherein the at least one modified D-amino acid is an azide-modified, an alkyne-modified, or a norbornene-modified D-amino acid.
A method of identifying an agent that inhibits peptidoglycan synthesis, the method comprising:
- a) contacting a bacterial cell in vitro with a test agent;
- and
- b) determining the effect, if any, of the test agent on incorporation of a modified D-amino acid into peptidoglycan in the bacterial cell;
- wherein a test agent that inhibits incorporation of the modified D-amino acid into peptidoglycan in the bacterial cell is considered a candidate agent for inhibiting peptidoglycan synthesis.
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-L1-Z-L2-Y
- wherein:
- PG is the modified peptidoglycan, L1 and L2 are independently optional linkers, Z is a heterocycle, and Y is a therapeutic agent or an immunomodulatory molecule;
- and
- b) a pharmaceutically acceptable excipient.
Dependencies are inferred from the claim text.