Background: Human serum albumin (HSA), the most abundant protein in plasma, is a monomeric multi-domain macromolecule with at least nine binding sites for endogenous and exogenous ligands. HSA displays an extraordinary ligand binding capacity as a depot and carrier for many compounds including most acidic drugs. Consequently, HSA has the potential to influence the pharmacokinetics and pharmacodynamics of drugs.

Objective: In this review, the structural determinants of drug binding to the multiple sites of HSA are analyzed and discussed in detail. Moreover, insight into the allosteric and competitive mechanisms underpinning drug recognition, delivery, and efficacy are analyzed and discussed.

Conclusion: As several factors can modulate drug binding to HSA (e.g., concurrent administration of drugs competing for the same binding site, ligand binding to allosteric-coupled clefts, genetic inherited diseases, and post-translational modifications), ligand binding to HSA is relevant not only under physiological conditions, but also in the pharmacological therapy management.

背景：人血清白蛋白（HSA）是血浆中最丰富的蛋白质，是一种单体多结构域大分子，具有至少9个内源和外源配体结合位点。HSA显示出非凡的配体结合能力，可作为许多化合物（包括大多数酸性药物）的储库和载体。因此，HSA有可能影响药物的药代动力学和药效学。

目的：在本综述中，将详细分析和讨论药物与HSA多个位点结合的结构决定因素。此外，分析和讨论了对支持药物识别，递送和功效的变构和竞争机制的见解。

结论：由于多种因素可调节药物与HSA的结合（例如，同时给药争夺相同结合位点的药物，配体与变构偶联的裂隙结合，遗传遗传疾病和翻译后修饰），配体与HSA的结合至关重要不仅在生理条件下，而且在药物治疗管理上。