Enhanced assembly stability for amine-based cationic glycolipid

IF 2.4 3区化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Carbohydrate Research Pub Date : 2024-07-29 DOI:10.1016/j.carres.2024.109224

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Abstract

Glycolipids incorporating positive charges, mediated by an imidazolium cation, have shown potential for effective formulation of vesicular drug carriers, reflecting repulsive electrostatic forces, promoting the formation of nanosized assemblies and preventing unwanted Oswald ripening (Goh et al. (2019), ACS Omega 4, 17,039). Our continuous development of an assembly-based drug delivery system prompted us to investigate a pH-sensitive analogue, leading to the synthesis of a 6-amino-Guerbet glycoside. However, in contrast to the imidazolium counterpart, the amine-mediated charge increased the intermolecular cohesions, furnishing bigger assemblies instead, which further increased upon introduction of acid. Moreover, assemblies exhibited a significantly reduced positive charge density. It is concluded that strong proton-initiated hydrogen bonding between amino groups provide cohesive head group interactions overcompensating possible repulsive charge interactions. While this behavior invalidates the application of the amino-glucoside as dispersing agent for the formulation of small vesicles, it potentially paves a route towards enhanced vesicle stability.

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增强胺基阳离子糖脂的组装稳定性。

在咪唑阳离子的介导下，含有正电荷的糖脂已显示出有效配制囊泡药物载体的潜力，它反映了排斥性静电力，促进了纳米级装配的形成，并防止了不必要的奥斯瓦尔德熟化（Goh 等人（2019），ACS Omega 4，17,039）。基于组装的给药系统的不断发展促使我们研究一种对 pH 值敏感的类似物，从而合成了一种 6-氨基格尔伯特苷。然而，与咪唑鎓类似物不同的是，胺介导的电荷增加了分子间的内聚力，从而产生了更大的组装体。此外，组装体的正电荷密度明显降低。由此得出结论，氨基之间由质子引发的强氢键提供了内聚的头基相互作用，弥补了可能存在的排斥电荷相互作用。虽然这种行为使氨基葡萄糖苷不能用作配制小囊泡的分散剂，但它有可能为提高囊泡的稳定性铺平道路。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Carbohydrate Research 化学-生化与分子生物学

CiteScore

5.00

自引率

3.20%

发文量

183

审稿时长

3.6 weeks

期刊介绍： Carbohydrate Research publishes reports of original research in the following areas of carbohydrate science: action of enzymes, analytical chemistry, biochemistry (biosynthesis, degradation, structural and functional biochemistry, conformation, molecular recognition, enzyme mechanisms, carbohydrate-processing enzymes, including glycosidases and glycosyltransferases), chemical synthesis, isolation of natural products, physicochemical studies, reactions and their mechanisms, the study of structures and stereochemistry, and technological aspects. Papers on polysaccharides should have a "molecular" component; that is a paper on new or modified polysaccharides should include structural information and characterization in addition to the usual studies of rheological properties and the like. A paper on a new, naturally occurring polysaccharide should include structural information, defining monosaccharide components and linkage sequence. Papers devoted wholly or partly to X-ray crystallographic studies, or to computational aspects (molecular mechanics or molecular orbital calculations, simulations via molecular dynamics), will be considered if they meet certain criteria. For computational papers the requirements are that the methods used be specified in sufficient detail to permit replication of the results, and that the conclusions be shown to have relevance to experimental observations - the authors'' own data or data from the literature. Specific directions for the presentation of X-ray data are given below under Results and "discussion".