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个人简介
Toll-like receptors (TLRs) are a family of conserved pattern recognition receptors (PRRs) that recognize pathogen associated molecular patterns and serve as primary sensors of the innate immune system. Ten members of the TLR family have so far been identified in the human genome. The ligands for these receptors are structurally highly conserved microbial molecules such as lipo- polysaccharides (LPS) (recognized by TLR4), lipopeptides (TLR2 in combination with TLR1 or TLR6), flagellin (TLR5), single stranded RNA (TLR7 and TLR8), double-stranded RNA (TLR3), CpG motif-containing DNA (TLR9) and profilin present on uropathogenic bacteria (TLR 11).The activation of PRRs by their cognate ligands leads to production of inflammatory cytokines, upregulation of MHC molecules and co-stimulatory signals in antigen-presenting cells as well as activating natural killer cells, in addition to priming and amplifying antigen-specific T-, and B-cell effector functions. Thus, these stimuli serve to link innate and adaptive immunity and can therefore be exploited as powerful adjuvants in eliciting both primary and anamnestic immune responses.
In this context, I have worked on the SAR studies of CLO75, a potent TLR-8 agonist (Org. Biomol. Chem. 2013, 11, 1179-98), synthesized furo[2,3-c]quinoline as exquisite TLR-8 agonist (J. Med. Chem. 2013, 56, 6871-85), synthesized 3-substituted quinoline-2-amine (ChemMedChem 2014, 4, 719-23) as specific TLR-8 agonist and finally synthesized open-chain quinoline analogues as exquisite TLR-8 specific agonist with augmented activity (J. Med. Chem. 2015, 58, 7833-49).
Endotoxin, or lipopolysaccharide (LPS), a structural component of the outer membrane of most gram-negative bacteria, plays a pivotal role in septic shock, a syndrome of systemic toxicity which occurs frequently as a sequel to serious systemic gram-negative infections. The activation by LPS of the innate immune response, mediated via toll-like receptor 4 (TLR4), leads to a dysregulated production of numerous inflammatory mediators. The resultant systemic inflammatory response progresses to the frequently fatal syndrome of multiple-system organ failure.
In this context, I have worked on the design and synthesis of lipopolyamines as an anti-sepsis agent. As a post-doc, I have developed the lead molecule DS-96 (Antimicrob. Agents Chemother. 2007, 51: 2811-2819) as an antisepsis agent and worked on its prodrug approach to eliminate its toxicity. At the same time, analogues of DS-96 were synthesized and screened for TLR-4 inhibition assay (Bioorg. Med. Chem. 2009, 17(2), 709-15; Bioorg. Med. Chem. Lett. 2009, 19(9), 2478-81).
I am currently working on the design, characterization and synthesis of prodrugs of polyamines to use them as nanoparticles using different polymers for efficient drug delivery of siRNA and micro RNA for treatment of different types of tumors.
研究兴趣
论文共 45 篇作者统计合作学者相似作者
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Rongguo Ren,Xiaofang Wang,Derek A Leas,Christian Scheurer, Sarah Hoevel,Monica Cal,Gong Chen,Longjin Zhong,Kasiram Katneni,Thao Pham,Rahul Patil,Diptesh Sil,Matthias J Walters,Thomas T Schulze,Andrew J Neville,Yuxiang Dong,Sergio Wittlin,Marcel Kaiser,Paul H Davis,Susan A Charman,Jonathan L Vennerstrom
ACS symposium seriespp.163-196, (2022)
Biomaterials advances (2022): 212755-212755
Biomaterials advances (2022): 213236-213236
Journal of Controlled Release (2021): 139-150
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#Papers: 45
#Citation: 675
H-Index: 16
G-Index: 24
Sociability: 5
Diversity: 0
Activity: 0
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