Amaral Luísa M P F, Moniz Tânia, Rangel Maria
REQUIMTE, LAQV, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, R. do Campo Alegre, 4169-007 Porto, Portugal.
REQUIMTE, LAQV, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
Molecules. 2024 Dec 14;29(24):5905. doi: 10.3390/molecules29245905.
In this study, we synthesized a series of 3-hydroxy-4-pyridinone (3,4-HPO) chelators with varying lipophilicity by modifying the length of their alkyl chains. To investigate their interaction with lipid membranes, we employed differential scanning calorimetry (DSC) and electron paramagnetic resonance (EPR) spectroscopy using dimyristoylphosphatidylcholine (DMPC) and palmitoyloleoylphosphatidylcholine (POPC) liposomes as membrane model systems. DSC experiments on DMPC liposomes revealed that hexyl-substituted chelators significantly altered the thermotropic phase behavior of the lipid bilayer, indicating their potential as membrane property modulators. EPR studies on DMPC and POPC liposomes provided detailed insights into the depth-dependent effects of chelators on membrane fluidity. Our findings highlight the crucial role of alkyl chain length in determining the interaction of 3,4-HPO chelators with lipid membranes and offer valuable insights for the design of lipid-interacting therapeutic agents based on this scaffold.
在本研究中，我们通过改变烷基链的长度，合成了一系列具有不同亲脂性的3-羟基-4-吡啶酮（3,4-HPO）螯合剂。为了研究它们与脂质膜的相互作用，我们使用二肉豆蔻酰磷脂酰胆碱（DMPC）和棕榈酰油酰磷脂酰胆碱（POPC）脂质体作为膜模型系统，采用差示扫描量热法（DSC）和电子顺磁共振（EPR）光谱法。对DMPC脂质体的DSC实验表明，己基取代的螯合剂显著改变了脂质双层的热致相行为，表明它们具有作为膜性质调节剂的潜力。对DMPC和POPC脂质体的EPR研究提供了关于螯合剂对膜流动性的深度依赖性影响的详细见解。我们的研究结果突出了烷基链长度在决定3,4-HPO螯合剂与脂质膜相互作用中的关键作用，并为基于该支架设计与脂质相互作用的治疗剂提供了有价值的见解。
