Dataset Information

Synthesis and Application of Methyl N,O-Hydroxylamine Muramyl Peptides.

ABSTRACT: 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-?B) 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.

SUBMITTER: Lazor KM

PROVIDER: S-EPMC6625359 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Synthesis and Application of Methyl N,O-Hydroxylamine Muramyl Peptides.

Lazor Klare M KM Zhou Junhui J DeMeester Kristen E KE D'Ambrosio Elizabeth A EA Grimes Catherine L CL

Chembiochem : a European journal of chemical biology 20190321 11

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-hydroxylami ...[more]

PMID: 30672111

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Project description:The photodissociation of small molecules has been extensively studied because of the increase in environmental problems related to the atmosphere of the Earth. In this work, the photodissociation mechanisms of hydroxylamine (NH2OH) as a model molecule in its lowest singlet-excited (S1) state were systematically studied using the complete active space second-order perturbation theory (CASPT2) and transition state theory (TST). In particular, this study focused on nonradiative relaxation processes that convert the S0 → S1 excited-state molecule to its products in their respective electronic ground states. The potential energy curves obtained from relaxed scans suggest that O-H dissociation is the preferred process in the S1 state. For the N-O and N-H dissociation pathways, thermally excited precursors were hypothesized to form in the S0 state to circumvent O-H dissociation. Thus, S0 → S1 vertical excitations lead to transition structures in the S1 state, which fragment to their respective electronic-ground-state products. The thermodynamic and kinetic results confirmed the precursor hypothesis, showing that the exothermic energy caused by the formation of HNO and H2 is sufficient to generate such precursors in the S0 state. Additionally, the TST confirmed that unimolecular isomerization-dissociation is a two-step process that generates products effectively by direct photolysis of the corresponding covalent bonds. In particular, the process consists of O-H bond dissociation, followed by spontaneous isomerization and formation of H2 in its electronic ground state, resulting in the high quantum yield observed in the UV absorption experiments in the preferential formation of HNO and H2. The configuration interaction coefficients of the characteristic structures on the potential energy curves revealed considerable changes in the multiconfigurational character of the wavefunctions, especially for the transition structures. These are characterized by the development of Rydberg orbitals, being produced at the intersection of the S0 and S1 states. The present study highlights the effects of thermal selectivity and the multiconfigurational character of the wavefunctions on photodissociation. Because detailed information on the photolytic mechanisms of isolated NH2OH is limited both theoretically and experimentally, these results provide fundamental insight into unimolecular photodissociation, posing ground for future studies on related systems.

Dataset Information

Synthesis and Application of Methyl N,O-Hydroxylamine Muramyl Peptides.

Publications

Synthesis and Application of Methyl N,O-Hydroxylamine Muramyl Peptides.

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