Balleza Daniel
Laboratorio de Microbiología, Unidad de Investigación y Desarrollo en Alimentos, Instituto Tecnológico de Veracruz, Tecnológico Nacional de México, Veracruz 91897, Mexico.
Antibiotics (Basel). 2025 Apr 22;14(5):422. doi: 10.3390/antibiotics14050422.
The formation of aqueous pores through the interaction of amphipathic peptides is a process facilitated by the conformational dynamics typical of these biomolecules. Prior to their insertion with the membrane, these peptides go through several conformational states until they finally reach a stable α-helical structure. The conformational dynamics of these pore-forming peptides, α-PFP, is, thus, encoded in their amino acid sequence, which also predetermines their intrinsic flexibility. However, although the role of flexibility is widely recognized as fundamental in their bioactivity, it is still unclear whether this parameter is indeed decisive, as there are reports favoring the view of highly disruptive flexible peptides and others where relative rigidity also predetermines high rates of permeability across membranes. In this review we discuss in depth all those aspects linked to the conformational dynamics of these small biomolecules and which depend on the composition, sequence and dynamic performance both in aqueous phase and in close interaction with phospholipids. In addition, evidence is provided for the contribution of the known carboxyamidation in some well-studied α-PFPs, which are preferentially associated with sequences intrinsically more rigid than those not amidated and generally more flexible than the former. Taken together, this information is of great relevance for the optimization of new antibiotic peptides.
两亲性肽相互作用形成水通道是一个由这些生物分子典型的构象动力学促进的过程。在插入膜之前，这些肽会经历几种构象状态，直到最终达到稳定的α-螺旋结构。因此，这些成孔肽α-PFP的构象动力学编码在它们的氨基酸序列中，这也预先决定了它们固有的柔韧性。然而，尽管柔韧性的作用在其生物活性中被广泛认为是至关重要的，但这个参数是否真的起决定性作用仍不清楚，因为有报道支持高度破坏的柔性肽的观点，也有报道表明相对刚性也预先决定了跨膜高渗透率。在这篇综述中，我们深入讨论了与这些小生物分子构象动力学相关的所有方面，这些方面取决于它们在水相以及与磷脂紧密相互作用中的组成、序列和动态性能。此外，还提供了证据证明在一些经过充分研究的α-PFP中已知的羧基酰胺化的作用，这些α-PFP优先与本质上比未酰胺化的序列更刚性且通常比前者更柔性的序列相关联。综上所述，这些信息对于新型抗生素肽的优化具有重要意义。
