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Synthesis and Application of Methyl N,O ‐Hydroxylamine Muramyl Peptides
Author(s) -
Lazor Klare M.,
Zhou Junhui,
DeMeester Kristen E.,
D'Ambrosio Elizabeth A.,
Grimes Catherine L.
Publication year - 2019
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201800731
Subject(s) - muramyl dipeptide , peptidoglycan , bioconjugation , hydroxylamine , nod2 , innate immune system , chemistry , biochemistry , linker , cathelicidin , stereochemistry , cell wall , in vitro , receptor , computer science , operating system
The innate immune system's interaction with bacterial cells plays a pivotal role in a variety of human diseases. Carbohydrate units derived from a component of bacterial cell wall, peptidoglycan (PG), are known to stimulate an immune response. Nonetheless, access to modified late‐stage peptidoglycan intermediates is limited due to their synthetic complexity. A method to rapidly functionalize PG fragments is needed to better understand the natural host–PG interactions. Here methyl N,O ‐hydroxylamine linkers are incorporated onto a synthetic PG derivative, muramyl dipeptide (MDP). The modification of MDP maintained the ability to stimulate a nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) immune response dependent on the expression of nucleotide‐binding oligomerization domain‐containing protein 2 (Nod2). Intrigued by this modification's maintenance of biological activity, several applications were explored. Methyl N,O ‐hydroxylamine MDP was amendable to N ‐hydroxylsuccinimide (NHS) chemistry for bioconjugation to fluorophores as well as a self‐assembled monolayer for Nod2 surface plasmon resonance analysis. Finally, linker incorporation was applicable to larger PG fragments, both enzymatically generated from Escherichia coli or chemically synthesized. This methodology provides rapid access to PG probes in one step and allows for the installation of a variety of chemical handles to advance the molecular understanding of PG and the innate immune system.