scholarly journals Ortho -Substituted lipidated Brartemicin derivative shows promising Mincle-mediated adjuvant activity

2020 ◽  
Author(s):  
Amy Foster ◽  
Kristel Kodar ◽  
Mattheus Timmer ◽  
Bridget Stocker
Keyword(s):  
Inflammatory Response ◽  
Biological Evaluation ◽  
Vaccine Adjuvants ◽  
Human Origin ◽  
Efficient Synthesis ◽  
Adjuvant Activity ◽  
Promising Target ◽  
Pathogen Recognition Receptor ◽  
Recognition Receptor ◽  
Better Than

This journal is © The Royal Society of Chemistry. The macrophage inducible C-type lectin (Mincle) is a pathogen recognition receptor (PRR) that is a promising target for the development of Th1-polarising vaccine adjuvants. We recently reported on the synthesis and evaluation of lipidated Brartemicin analogues that showed Mincle agonist activity, with our lead agonist exhibiting potent Th1 adjuvant activity that was greater than that of trehalose dibehenate (TDB). Herein, we report on the efficient synthesis and subsequent biological evaluation of additional lipidated Brartemicin analogues that were designed to determine the structural requirements for optimal Mincle signalling. While all the Brartemicin analogues retained their ability to signal through Mincle and induce a functional response, the o-substituted and m,m-disubstituted derivatives (5a and 5d, respectively) induced a potent inflammatory response when using cells of both murine and human origin, with this response being the greatest observed thus far. As the inflammatory response elicited by 5a was slightly better than that induced by 5d, our findings point to o-substituted Brartemicin analogues as the preferred scaffold for further adjuvant development.

scholarly journals Ortho -Substituted lipidated Brartemicin derivative shows promising Mincle-mediated adjuvant activity

2020 ◽  
Author(s):  
Amy Foster ◽  
Kristel Kodar ◽  
Mattheus Timmer ◽  
Bridget Stocker
Keyword(s):  
Inflammatory Response ◽  
Biological Evaluation ◽  
Vaccine Adjuvants ◽  
Human Origin ◽  
Efficient Synthesis ◽  
Adjuvant Activity ◽  
Promising Target ◽  
Pathogen Recognition Receptor ◽  
Recognition Receptor ◽  
Better Than

This journal is © The Royal Society of Chemistry. The macrophage inducible C-type lectin (Mincle) is a pathogen recognition receptor (PRR) that is a promising target for the development of Th1-polarising vaccine adjuvants. We recently reported on the synthesis and evaluation of lipidated Brartemicin analogues that showed Mincle agonist activity, with our lead agonist exhibiting potent Th1 adjuvant activity that was greater than that of trehalose dibehenate (TDB). Herein, we report on the efficient synthesis and subsequent biological evaluation of additional lipidated Brartemicin analogues that were designed to determine the structural requirements for optimal Mincle signalling. While all the Brartemicin analogues retained their ability to signal through Mincle and induce a functional response, the o-substituted and m,m-disubstituted derivatives (5a and 5d, respectively) induced a potent inflammatory response when using cells of both murine and human origin, with this response being the greatest observed thus far. As the inflammatory response elicited by 5a was slightly better than that induced by 5d, our findings point to o-substituted Brartemicin analogues as the preferred scaffold for further adjuvant development.

scholarly journals ER Stress, UPR Activation and the Inflammatory Response to Viral Infection

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 798
Author(s):  
Mara Cirone
Keyword(s):  
Inflammatory Response ◽  
Viral Infection ◽  
Viral Infections ◽  
Protective Role ◽  
Microbial Infection ◽  
Unfolded Protein ◽  
Cytokines And Chemokines ◽  
Complex Process ◽  
Protein Response ◽  
Recognition Receptor

The response to invading pathogens such as viruses is orchestrated by pattern recognition receptor (PRR) and unfolded protein response (UPR) signaling, which intersects and converges in the activation of proinflammatory pathways and the release of cytokines and chemokines that harness the immune system in the attempt to clear microbial infection. Despite this protective intent, the inflammatory response, particularly during viral infection, may be too intense or last for too long, whereby it becomes the cause of organ or systemic diseases itself. This suggests that a better understanding of the mechanisms that regulate this complex process is needed in order to achieve better control of the side effects that inflammation may cause while potentiating its protective role. The use of specific inhibitors of the UPR sensors or PRRs or the downstream pathways activated by their signaling could offer the opportunity to reach this goal and improve the outcome of inflammation-based diseases associated with viral infections.

scholarly journals Triazolbenzo[d]thiazoles: Efficient synthesis and biological evaluation as neuroprotective agents

2012 ◽  
Vol 22 (18) ◽  
pp. 5976-5978 ◽  
Author(s):  
Belem Avila ◽  
Aaron Roth ◽  
Heather Streets ◽  
Donard S. Dwyer ◽  
Mark J. Kurth
Keyword(s):  
Biological Evaluation ◽  
Neuroprotective Agents ◽  
Efficient Synthesis ◽  
Synthesis And Biological Evaluation

Enantioselective synthesis of (R)-tolterodine using lithiation/borylation–protodeboronation methodology

2012 ◽  
Vol 90 (11) ◽  
pp. 965-974 ◽  
Author(s):  
Stefan Roesner ◽  
Varinder K. Aggarwal
Keyword(s):  
Enantioselective Synthesis ◽  
High Yield ◽  
Magnesium Bromide ◽  
Efficient Synthesis ◽  
Boronic Ester ◽  
Better Than

The synthesis of the pharmaceutical (R)-tolterodine is reported using lithiation/borylation–protodeboronation of a homoallyl carbamate as the key step. This step was tested with two permutations: an electron-neutral aryl Li-carbamate reacting with an electron-rich boronic ester and an electron-rich aryl Li-carbamate reacting with an electron-neutral boronic ester. It was found that the latter arrangement was considerably better than the former. Further improvements were achieved using magnesium bromide in methanol leading to a process that gave high yield and high enantioselectivity in the lithiation/borylation reaction. The key step was used in an efficient synthesis of (R)-tolterodine in a total of eight steps in a 30% overall yield and 90% ee.

ChemInform Abstract: Efficient Synthesis and Biological Evaluation of 1,2,9-Trisubstituted 1,9-Dihydro-6H-purin-6-ones.

ChemInform ◽  
2009 ◽  
Vol 40 (25) ◽  
Author(s):  
Nian-Yu Huang ◽  
Yong-Ju Liang ◽  
Ming-Wu Ding ◽  
Li-Wu Fu ◽  
Hong-Wu He
Keyword(s):  
Biological Evaluation ◽  
Efficient Synthesis ◽  
Synthesis And Biological Evaluation

Efficient Synthesis and Biological Evaluation of 5′-GalNAc Conjugated Antisense Oligonucleotides

2015 ◽  
Vol 26 (8) ◽  
pp. 1451-1455 ◽  
Author(s):  
Michael E. Østergaard ◽  
Jinghua Yu ◽  
Garth A. Kinberger ◽  
W. Brad Wan ◽  
Michael T. Migawa ◽  
...  
Keyword(s):  
Antisense Oligonucleotides ◽  
Biological Evaluation ◽  
Efficient Synthesis ◽  
Synthesis And Biological Evaluation

scholarly journals Avian Pattern Recognition Receptor Sensing and Signaling

2020 ◽  
Vol 7 (1) ◽  
pp. 14 ◽  
Author(s):  
Sabari Nath Neerukonda ◽  
Upendra Katneni
Keyword(s):  
Pattern Recognition ◽  
Rational Design ◽  
Animal Species ◽  
Critical Role ◽  
Functional Characterization ◽  
Structural Features ◽  
Present Review ◽  
Vaccine Adjuvants ◽  
Microbial Defense ◽  
Recognition Receptor

Pattern recognition receptors (PRRs) are a class of immune sensors that play a critical role in detecting and responding to several conserved patterns of microorganisms. As such, they play a major role in the maintenance of immune homeostasis and anti-microbial defense. Fundamental knowledge pertaining to the discovery of PRR functions and their ligands continue to advance the understanding of immune system and disease resistance, which led to the rational design and/or application of various PRR ligands as vaccine adjuvants. In addition, the conserved nature of many PRRs throughout the animal kingdom has enabled the utilization of the comparative genomics approach in PRR identification and the study of evolution, structural features, and functions in many animal species including avian. In the present review, we focused on PRR sensing and signaling functions in the avian species, domestic chicken, mallard, and domestic goose. In addition to summarizing recent advances in the understanding of avian PRR functions, the present review utilized a comparative biology approach to identify additional PRRs, whose functions have been well studied in mammalians but await functional characterization in avian.

scholarly journals The Sulfated Polysaccharides of Brown Algae and Products of Their Enzymatic Transformation as Potential Vaccine Adjuvants

2018 ◽  
Vol 13 (8) ◽  
pp. 1934578X1801300 ◽  
Author(s):  
Tatyana A. Kuznetsova ◽  
Elena V. Persiyanova ◽  
Svetlana P. Ermakova ◽  
Maxim Yu. Khotimchenko ◽  
Natalya N. Besednova
Keyword(s):  
Immune Response ◽  
Brown Algae ◽  
Complex Structure ◽  
Physicochemical Characteristics ◽  
Sulfated Polysaccharides ◽  
Vaccine Adjuvants ◽  
Adjuvant Activity ◽  
Humoral Immune ◽  
Enzymatic Transformation ◽  
Immunomodulatory Action

The review is devoted to critical analysis of literature data, deal with effects and mechanisms of action of sulfated polysaccharides (PSs) – fucoidans from brown algae and products of their enzymatic transformation as potential adjuvants for enhancement of anti-infective and antitumor immune response. Numerous experimental data indicate that sulfated PSs demonstrate properties of vaccine adjuvants. Application perspectiveness of fucoidans as vaccine adjuvants is defined by their high biocompatibility, low-toxicity, safety and good tolerance by macroorganism, and also mechanisms of their immunomodulatory action. In particular, fucoidans are agonists of receptors of innate immunity and strong inducers of cellular and humoral immune response. At presenting the data of structural - functional interrelations, attention focused to the defining role of degree of sulfation, uronic acids and polyphenols contents, and also molecular mass in actions of fucoidans to innate and adaptive immunity cells. Insufficiency of literary data on studying of correlation of structure – physicochemical characteristics with adjuvanticities of the sulfated PSs, and also the problem of standardization of their active fractions are noted. Special attention is paid to the analysis of immunomodulatory and adjuvant activity of fucoidan oligosaccharides. Presented here results of experimental trial indicate that, despite the difficulties due to preparation of highly purified structurally characterized fractions and complex structure of fucoidans, these substances can be used as safe and effective adjuvants in vaccines against various pathogens including viruses, and also in antitumor vaccines.

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