TLR2 Agonistic Small Molecules: Detailed Structure–Activity Relationship, Applications, and Future Prospects,Journal of Medicinal Chemistry

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TLR2 Agonistic Small Molecules: Detailed Structure–Activity Relationship, Applications, and Future Prospects
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2020-12-21 , DOI: 10.1021/acs.jmedchem.0c01627
Arshpreet Kaur ₁ , Deepender Kaushik ₁ , Sakshi Piplani _{2,

3} , Surinder K. Mehta ₁ , Nikolai Petrovsky _{2,

3} , Deepak B. Salunke _{1,

4}

Affiliation

Toll-like receptors (TLRs) are the pattern recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) in microbial species. Among the various TLRs, TLR2 has a special place due to its ability to sense the widest repertoire of PAMPs owing to its heterodimerization with either TLR1 or TLR6, broadening its ligand diversity against pathogens. Various scaffolds are reported to activate TLR2, which include naturally occurring lipoproteins, synthetic lipopeptides, and small heterocyclic molecules. We described a detailed SAR in TLR2 agonistic scaffolds and also covered the design and chemistry for the conjugation of TLR2 agonists to antigens, carbohydrates, polymers, and fluorophores. The approaches involved in delivery of TLR2 agonists such as lipidation of antigen, conjugation to polymers, phosphonic acids, and other linkers to achieve surface adsorption, liposomal formulation, and encapsulating nanoparticles are elaborated. The crystal structure analysis and computational modeling are also included with the structural features that facilitate TLR2 activation.

中文翻译：

TLR2拮抗小分子：详细的结构-活性关系，应用和未来前景

Toll样受体（TLR）是识别微生物物种中病原体相关分子模式（PAMP）的模式识别受体（PRR）。在各种TLR中，由于TLR2与TLR1或TLR6异源二聚化，从而能够感知最广泛的PAMP，从而具有针对病原体的配体多样性，因此它具有特殊的地位。据报道，多种支架可激活TLR2，包括天然存在的脂蛋白，合成脂肽和小的杂环分子。我们在TLR2激动剂支架中描述了详细的SAR，并且还涵盖了TLR2激动剂与抗原，碳水化合物，聚合物和荧光团结合的设计和化学方法。TLR2激动剂的递送方法包括抗原脂化，与聚合物结合，膦酸，并详细描述了实现表面吸附，脂质体配制和包封纳米颗粒的其他连接体。晶体结构分析和计算模型也包括有助于TLR2激活的结构特征。

更新日期：2021-01-14

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