两种基于脂质A的TLR4激动剂的生物和合成形式的物理化学表征
Gang Hu1, David J Varisco2, Sayan Das2
1Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66047, USA.
Heliyon
|July 24, 2023
概括
新型托尔类受体 (TLR) 激动剂BECC438和BECC470已被开发用于增强的疫苗辅助剂. 生物物理特征和配方研究表明它们的潜力,BECC470s作为TLR4激动剂,尽管内毒素检测低.
科学领域:
- 免疫学 免疫学 免疫学
- 疫苗学 疫苗学 疫苗学
- 生物化学 生化学
背景情况:
- 收费类受体 (TLR) 激动剂是授权疫苗中重要的免疫增强辅助剂.
- 单酸脂A (MPL®) 是一种经批准的TLR4激动剂,但其生物起源呈现异质性.
- 需要更安全,更强效和化学定义的辅助剂.
研究的目的:
- 通过使用细菌酶组合化学 (BECC) 平台开发的新型TLR4激素候选者BECC438和BECC470的特征.
- 评估这些合成脂质A类别的生物物理性质和配方潜力.
- 评估它们作为疫苗辅助剂的有效性.
主要方法:
- 纯化和化学合成BECC438和BECC470 (生物:BECC438b,BECC470b;合成:BECC438s,BECC470s) 的方法.
- 详细的生物物理特征,包括相位过渡温度和酸盐组的水合.
- 使用Alhydrogel和Medimmune Emulsion (ME) 的配方研究;使用基于细胞的系统和Limulus amebocyte lysate (LAL) 试验评估TLR4激动性.
主要成果:
- 合成的BECC438s和BECC470s具有相同的乙链;BECC438s是二酸化的,BECC470s是单酸化的.
- 在生物和合成形式之间观察到相位过渡温度和酸盐水合的显著差异.
- 所有类似物都成功配制了Alhydrogel或ME; BECC470s显示了最小的LAL信号,但保留了TLR4激动剂活性.
结论:
- 化学合成的BECC438和BECC470是明确的TLR4激动剂,与其生物对应物相比,具有独特的生物物理性质.
- 这些新型激动剂显示出有前途的辅助作用潜力,可以有效地配制用于疫苗应用.
- 进一步优化这些有前途的TLR4激动因子的疫苗开发是有必要的.
更多相关视频
09:51Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling
Published on: July 26, 2017
12.4K
08:46Cell-Free Production of Proteoliposomes for Functional Analysis and Antibody Development Targeting Membrane Proteins
Published on: September 22, 2020
3.9K
相关概念视频
Formation of Lipopolysaccharides
48
Lipopolysaccharides (LPS) are crucial components of the outer membrane of Gram-negative bacteria, serving both structural and functional roles. It contributes to membrane stability and protects bacteria from host immune responses. LPS is composed of three major regions—lipid A, a core oligosaccharide, and an O antigen. The biosynthesis and assembly of LPS involve a highly coordinated set of enzymatic reactions and transport mechanisms. Additionally, LPS is recognized as an endotoxin,...
48
The Two-State Receptor Model
2.0K
The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
The binding affinity of a drug determines its interaction with...
The binding affinity of a drug determines its interaction with...
2.0K
Biosynthesis of Lipids
40
Microbial membranes exhibit remarkable diversity in lipid composition, reflecting evolutionary adaptations to various environmental conditions. The three domains of life—Bacteria, Archaea, and Eukarya—synthesize membrane lipids through distinct biosynthetic pathways, leading to fundamental structural differences that impact membrane stability, function, and adaptability.Fatty Acid-Based Lipids in Bacteria and EukaryaBacteria and eukaryotes share a common fatty acid biosynthesis...
40
Adrenergic Agonists: Chemistry and Structure-Activity Relationship
3.1K
Adrenergic agonists' structure-activity relationship (SAR) determines their selectivity and efficacy. These agonists comprise a phenylethylamine moiety with an aromatic ring and an ethylamine side chain.
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...
3.1K
