Guimarães Carlos F R C, Félix Amanda S, Brandão Tiago A S, Bemquerer Marcelo P, Piló-Veloso Dorila, Verly Rodrigo M, Resende Jarbas M
Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, P.O. Box 486, Belo Horizonte, MG, 31270-901, Brazil.
Present Address: Universidade Nilton Lins, Avenida Professor Nilton Lins, Manaus, AM, 69058-030, Brazil.
Amino Acids. 2023 Sep;55(9):1201-1212. doi: 10.1007/s00726-023-03309-x. Epub 2023 Aug 6.
Peptides are remarkably interesting alternatives to several applications. In particular, antimicrobial sequences have raised major interest of the scientific community due to the resistance acquired by commonly used antibiotics. Amongst these, some dimeric peptides have shown very promising characteristics as strong biological activities and resistance against degradation by peptidases. However, despite such promising characteristics, a relatively small number of studies address dimeric peptides, mainly due to the synthesis-related obstacles in their production, whereas the well-implemented routines of solid phase peptide synthesis-which includes the possibility of automation-makes life significantly easier. Here, we present kinetic investigations of the dimerization of a cysteine-containing sequence to obtain the homodimeric antimicrobial peptide homotarsinin. Based on the structural and membrane interaction data already available for the dimer and its monomeric chain, we have proposed distinct dimerization protocols in selected environments, namely, aqueous buffer, TFE:HO and micellar solutions. The experimental results were adjusted by a theoretical model. Both the kinetic profiles and the reaction yields are dependent on the reaction medium, clearly indicating that aggregation, peptide structure, and peptide-membrane interactions play major roles in the formation of the disulfide bond. Finally, the rationalization of the different aspects addressed here is expected to contribute to research and applications that demand the obtainment of dimeric peptides.
肽在多种应用中是非常有趣的替代物。特别是，由于常用抗生素产生的耐药性，抗菌序列引起了科学界的极大兴趣。其中，一些二聚体肽表现出非常有前景的特性，如强大的生物活性和对肽酶降解的抗性。然而，尽管有这些有前景的特性，但针对二聚体肽的研究相对较少，主要是因为其生产过程中存在与合成相关的障碍，而成熟的固相肽合成常规方法（包括自动化的可能性）使操作变得容易得多。在这里，我们展示了对含半胱氨酸序列二聚化以获得同型二聚体抗菌肽同型塔西尼宁的动力学研究。基于已有的关于二聚体及其单体链的结构和膜相互作用数据，我们在选定的环境中，即水性缓冲液、TFE:HO和胶束溶液中，提出了不同的二聚化方案。实验结果通过理论模型进行了调整。动力学曲线和反应产率都取决于反应介质，清楚地表明聚集、肽结构和肽-膜相互作用在二硫键形成中起主要作用。最后，这里所探讨的不同方面的合理化有望有助于需要获得二聚体肽的研究和应用。
