Department of Molecular Sciences and Nanosystems, Ca' Foscari University of Venice, Via Torino 155, 30172 Venice, Italy.
Department of Molecular Sciences and Nanosystems, Ca' Foscari University of Venice, Via Torino 155, 30172 Venice, Italy; AXES Research Group, Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp, Belgium.
J Control Release. 2022 Aug;348:115-126. doi: 10.1016/j.jconrel.2022.05.038. Epub 2022 Jun 3.
Human serum albumin (hSA) is the major carrier protein for fatty acids (FAs) in plasma. Its ability to bind multiple FA moieties with moderate to high affinity has inspired the use of FA conjugation as a safe and natural platform to generate long-lasting therapeutics with enhanced pharmacokinetic properties and superior efficacy. In this frame, the choice of the FA is crucial and a comprehensive elucidation of the molecular interactions of FAs with hSA cannot be left out of consideration. To this intent, we report here a comparative analysis of the binding mode of different FA moieties with hSA. The choice among different albumin-binding FAs and how this influence the pharmacokinetics properties of a broad spectrum of therapeutic molecules will be discussed including a critical description of some clinically relevant FA conjugated therapeutics.
人血清白蛋白（hSA）是血浆中脂肪酸（FAs）的主要载体蛋白。其能够与多个 FA 部分以中等至高亲和力结合的能力启发了 FA 缀合的使用，将其作为一种安全和天然的平台，用于生成具有增强的药代动力学特性和更高疗效的长效治疗药物。在这种情况下，FA 的选择至关重要，并且不能不考虑对 FA 与人血清白蛋白相互作用的分子机制进行全面阐明。为此，我们在这里报告了不同 FA 部分与人血清白蛋白结合模式的比较分析。不同白蛋白结合 FA 的选择以及这种选择如何影响广泛治疗分子的药代动力学特性将被讨论，包括对一些临床相关 FA 缀合治疗药物的批判性描述。
