scholarly journals Advances in Desmuramyl Peptide Research

2019 ◽  
Vol 92 (2) ◽  
pp. 153-161 ◽  
Author(s):  
Rosana Ribić ◽  
Marija Paurević ◽  
Srđanka Tomić
Keyword(s):  
Structural Unit ◽  
Muramyl Dipeptide ◽  
Receptor Activation ◽  
Pharmacological Properties ◽  
Future Design ◽  
Immune Adjuvants ◽  
Dipeptide Analogues ◽  
Pathogen Recognition Receptor ◽  
Multiple Pathogen ◽  
Recognition Receptor

Immune adjuvants are added to vaccines in order to enhance the immune response to an antigen. Muramyl dipeptide, N-acetylmuramyl-L-alanyl-D-isoglutamine, is the smallest structural unit of peptidoglycans showing the immunostimulating activity. Muramyl dipeptide analogues without the hydrophilic N-acetylmuramyl moiety are called desmuramyl peptides. Here, we provide review of desmuramyl peptides which were synthesized in order to improve the pharmacological properties of parent muramyl dipeptide, including our results regarding adamantane containing derivatives. Approach for future design of novel immunostimulators based on multiple pathogen recognition receptor activation was also considered.

Muramyl-dipeptide analogues: Synthesis and biological activities

1988 ◽  
Vol 53 (11) ◽  
pp. 2897-2906 ◽  
Author(s):  
Jan Ježek ◽  
Milan Zaoral ◽  
Miloš Buděšínský ◽  
Jiří Günther ◽  
Jiří Rotta
Keyword(s):  
Biological Activities ◽  
Muramyl Dipeptide ◽  
Delayed Hypersensitivity ◽  
Test Compound ◽  
Active Compounds ◽  
Dipeptide Analogues ◽  
Pyrogenic Activity

In the search for immunoadjuvant active compounds without pyrogenic activity we prepared N-Ac-norMur-L-Abu-D-Gln-O-Bu (V), N-Ac-Mur-L-Abu-D-Gln-O-Bu (VII) and their respective α-benzylglycosides VI and VIII. All the prepared compounds are nonpyrogenic. In the delayed hypersensitivity test, compound V is inactive, VI is comparable to MDP, VII is more and VIII is less active than MDP.

scholarly journals Hsa-miR-99b/let-7e/miR-125a Cluster Regulates Pathogen Recognition Receptor-Stimulated Suppressive Antigen-Presenting Cells

2018 ◽  
Vol 9 ◽  
Author(s):  
Dagmar Hildebrand ◽  
Mariel-Esther Eberle ◽  
Sabine Marie Wölfle ◽  
Franziska Egler ◽  
Delal Sahin ◽  
...  
Keyword(s):  
Antigen Presenting Cells ◽  
Pathogen Recognition ◽  
Antigen Presenting ◽  
Pathogen Recognition Receptor ◽  
Recognition Receptor

scholarly journals Insights into the molecular basis of the NOD2 signalling pathway

Open Biology ◽  
2014 ◽  
Vol 4 (12) ◽  
pp. 140178 ◽  
Author(s):  
Joseph P. Boyle ◽  
Rhiannon Parkhouse ◽  
Tom P. Monie
Keyword(s):  
Pattern Recognition ◽  
Muramyl Dipeptide ◽  
Pattern Recognition Receptor ◽  
Cellular Proteins ◽  
Inflammatory Disorder ◽  
Downstream Effects ◽  
Susceptibility Factors ◽  
Inflammatory Bowel ◽  
Recognition Receptor

The cytosolic pattern recognition receptor NOD2 is activated by the peptidoglycan fragment muramyl dipeptide to generate a proinflammatory immune response. Downstream effects include the secretion of cytokines such as interleukin 8, the upregulation of pro-interleukin 1β, the induction of autophagy, the production of antimicrobial peptides and defensins, and contributions to the maintenance of the composition of the intestinal microbiota. Polymorphisms in NOD2 are the cause of the inflammatory disorder Blau syndrome and act as susceptibility factors for the inflammatory bowel condition Crohn's disease. The complexity of NOD2 signalling is highlighted by the observation that over 30 cellular proteins interact with NOD2 directly and influence or regulate its functional activity. Previously, the majority of reviews on NOD2 function have focused upon the role of NOD2 in inflammatory disease or in its interaction with and response to microbes. However, the functionality of NOD2 is underpinned by its biochemical interactions. Consequently, in this review, we have taken the opportunity to address the more ‘basic’ elements of NOD2 signalling. In particular, we have focused upon the core interactions of NOD2 with protein factors that influence and modulate the signal transduction pathways involved in NOD2 signalling. Further, where information exists, such as in relation to the role of RIP2, we have drawn comparison with the closely related, but functionally discrete, pattern recognition receptor NOD1. Overall, we provide a comprehensive resource targeted at understanding the complexities of NOD2 signalling.

scholarly journals Dissecting the allosteric networks governing agonist efficacy and potency in G protein-coupled receptors

2021 ◽  
Author(s):  
Franziska Marie Heydenreich ◽  
Maria Marti-Solano ◽  
Manbir Sandhu ◽  
Brian K Kobilka ◽  
Michel Bouvier ◽  
...  
Keyword(s):  
G Protein ◽  
Conformational Changes ◽  
Structural Changes ◽  
Receptor Activation ◽  
Residue Level ◽  
G Protein Coupled Receptors ◽  
Maximal Response ◽  
Pharmacological Properties ◽  
Receptor Ligand ◽  
G Protein Coupled

G protein-coupled receptors (GPCRs) translate binding of extracellular ligands into intracellular responses through conformational changes. Ligand properties are described by the maximum response (efficacy) and the agonist concentration at half-maximal response (potency). Integrating structural changes with pharmacological properties remains challenging and has not yet been performed at the resolution of individual amino acids. We use epinephrine and β2-adrenergic receptor as a model to integrate residue-level pharmacology data with intramolecular residue contact data describing receptor activation. This unveils the allosteric networks driving ligand efficacy and potency. We provide detailed insights into how structural rearrangements are linked to fundamental pharmacological properties at single-residue level in a receptor-ligand system. Our approach can be used to determine such pharmacological networks for any receptor-ligand complex.

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