AbstractA new strategy for the preparation of distinct N‐substituted muropeptides is described. Different orthogonally N‐protected disaccharide thioglycosides were designed and synthesized. Among them, compound 4, qualified as a key intermediate, was utilized for further chemical transformations to develop a series of diverse N‐substituted‐glucosaminyl N‐substituted‐muramyl dipeptides (GMDPs). These unique muropeptides were applied for the study of human NOD2 stimulation. Intriguingly, structural modification of the MurNAc residue to N‐non‐substituted muramic acid (MurNH2) in GMDP dramatically impaired NOD2 stimulatory activity, but GMDPs possessing the glucosamine residue with a free amino group retained NOD2 stimulation activity. This work is the first study to illustrate the impact of both N‐substituents of GMDPs on immunostimulatory activities of human NOD2.

28 Apr 2021·ACS Central ScienceQ1 · CHEMISTRY

Bacterial Peptidoglycan Fragments Differentially Regulate Innate Immune Signaling

Q1 · CHEMISTRY

ArticleOA

Author: Zagani, Rachid ; Reinecker, Hans-Christian ; Liu, Shuzhen ; Chen, Shuyuan ; Grimes, Catherine L. ; Mashayekh, Siavash ; Bersch, Klare L. ; DeMeester, Kristen E. ; Wodzanowski, Kimberly A.

The human innate immune system responds to both pathogen and commensal bacteria at the molecular level using bacterial peptidoglycan (PG) recognition elements. Traditionally, synthetic and commercially accessible PG monosaccharide units known as muramyl dipeptide (MDP) and N-glycolyl MDP (ng-MDP) have been used to probe the mechanism of innate immune activation of pattern recognition receptors, such as NOD-like receptors. However, bacterial PG is a dynamic and complex structure, with various chemical modifications and trimming mechanisms that result in the production of disaccharide-containing elements. These molecules pose as attractive targets for immunostimulatory screening; however, studies are limited because of their synthetic accessibility. Inspired by disaccharide-containing compounds produced from the gut microbe Lactobacillus acidophilus, a robust and scalable chemical synthesis of PG-based disaccharide ligands was implemented. Together with a monosaccharide PG library, compounds were screened for their ability to stimulate proinflammatory genes in bone-marrow-derived macrophages. The data reveal distinct gene induction patterns for monosaccharide and disaccharide PG units, suggesting that PG innate immune signaling is more complex than a one activator-one pathway program, as biologically relevant fragments induce transcriptional programs to different degrees. These disaccharide molecules will serve as critical immunostimulatory tools to more precisely define specialized innate immune regulatory mechanisms that distinguish between commensal and pathogenic bacteria residing in the microbiome.

01 Dec 2020·Biomedical Chromatography

Determination of the immunostimulatory drug—glucosoaminyl‐muramyl‐dipeptide—in human plasma using HPLC–MS/MS and its application to a pharmacokinetic study

Article

Author: Kuznetsov, Roman M. ; Moskaleva, Natalia E. ; Markin, Pavel A. ; Appolonova, Svetlana A. ; Andronova, Tatiana M.

AbstractGMDP (glucosoaminyl‐muramyl‐dipeptide), a synthetic analog of the peptidoglycan fragment of the bacterial cell wall, is an active component of the immunomodulatory drug Licopid. But the pharmacokinetic parameters of GMDP in humans after oral administration have not been investigated yet. The present study aimed at developing and validating a sensitive LC–MS/MS method for the analysis of GMDP in human plasma. The sample was prepared by solid‐phase extraction using Strata‐X 33 μm polymeric reversed‐phase 60 mg/3 mL cartridges Phenomenex (Torrance, CA, USA). The analytes were separated using an Acquity UPLC BEN C18 column, 1.7 μm 2.1 × 50 mm Waters (Milford, USA). GMDP and internal standard growth hormone releasing peptide‐2 (pralmorelin) were ionized in positive electrospray ionization mode and detected in multiple reaction monitoring mode. The developed method was validated within a linear range of 50–3000 pg/mL for GMDP. Accuracy for all analytes, given as the deviation between the nominal and measured concentration and assay variability , ranged from 1.61 to 3.02% and from 0.89 to 1.79%, respectively, for both within‐ and between‐run variabilities. The developed and validated HPLC–MS/MS method was successfully used to obtain the plasma pharmacokinetic profiles of GMDP distribution in human plasma.

100 Deals associated with Glycopin

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	L03	-

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Tuberculosis	Russia	-	17 Nov 1998
Respiratory Diseases	Russia	-	30 Jan 1998
Herpesviridae Infections	Russia	Teva Pharmaceutical Industries Ltd.	01 Sep 1996
Lung Diseases	Russia	Teva Pharmaceutical Industries Ltd.	01 Sep 1996
Psoriasis	Russia	Teva Pharmaceutical Industries Ltd.	01 Sep 1996
Pulmonary Tuberculosis	Russia	Teva Pharmaceutical Industries Ltd.	01 Sep 1996
Surgical Wound Infection	Russia	Teva Pharmaceutical Industries Ltd.	01 Sep 1996

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Anaphylaxis	Preclinical	Russia	Peoples' Friendship University of Russia	01 Feb 2019
Asthma	Preclinical	Russia	Peoples' Friendship University of Russia	01 Feb 2019
Rhinitis	Preclinical	Russia	Peoples' Friendship University of Russia	01 Feb 2019
Neutropenia	Discovery	Australia	-	-
Neutropenia	Discovery	Russia	-	-
Psoriasis	Discovery	United Kingdom	-	-
Pyoderma	Discovery	Russia	-	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis