Marziogiuseppe Gentile, Francesco Talotta, Jean Christophe Tremblay, Leticia González, Antonio Monari
{"title":"Predominant Binding Mode of Palmatine to DNA","authors":"Marziogiuseppe Gentile, Francesco Talotta, Jean Christophe Tremblay, Leticia González, Antonio Monari","doi":"10.1021/acs.jpclett.4c02721","DOIUrl":null,"url":null,"abstract":"Palmatine is a protoberberine alkaloid, which may produce singlet oxygen under visible light irradiation and binds to DNA. The fact that singlet oxygen activation in palmatine may be triggered by environmental conditions, and in particular its interaction with nucleic acids, makes it a most suitable candidate for photodynamic therapy and DNA-targeted noninvasive anticancer strategies. Despite these remarkable properties, the actual binding mode between palmatine and DNA has not been resolved, yet. Its elucidation has indeed led to contrasting hypotheses. In this contribution, by using long-range molecular dynamic simulations and enhanced sampling approaches, we unequivocally identify that intercalation is the dominant binding mode of palmatine with DNA, from both a thermodynamic and kinetic point of view.","PeriodicalId":62,"journal":{"name":"The Journal of Physical Chemistry Letters","volume":null,"pages":null},"PeriodicalIF":4.8000,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Journal of Physical Chemistry Letters","FirstCategoryId":"1","ListUrlMain":"https://doi.org/10.1021/acs.jpclett.4c02721","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
引用次数: 0
Abstract
Palmatine is a protoberberine alkaloid, which may produce singlet oxygen under visible light irradiation and binds to DNA. The fact that singlet oxygen activation in palmatine may be triggered by environmental conditions, and in particular its interaction with nucleic acids, makes it a most suitable candidate for photodynamic therapy and DNA-targeted noninvasive anticancer strategies. Despite these remarkable properties, the actual binding mode between palmatine and DNA has not been resolved, yet. Its elucidation has indeed led to contrasting hypotheses. In this contribution, by using long-range molecular dynamic simulations and enhanced sampling approaches, we unequivocally identify that intercalation is the dominant binding mode of palmatine with DNA, from both a thermodynamic and kinetic point of view.
巴马汀是一种原小檗碱,在可见光照射下可产生单线态氧,并与 DNA 结合。巴马汀的单线态氧活化可由环境条件触发,特别是它与核酸的相互作用,使其成为光动力疗法和 DNA 靶向非侵入性抗癌策略的最合适候选物质。尽管巴马汀具有这些非凡的特性,但它与 DNA 之间的实际结合模式尚未得到解决。对它的阐释确实导致了一些截然不同的假说。在这篇论文中,我们利用长程分子动力学模拟和增强采样方法,从热力学和动力学的角度明确指出,插层是巴马汀与 DNA 的主要结合模式。
期刊介绍:
The Journal of Physical Chemistry (JPC) Letters is devoted to reporting new and original experimental and theoretical basic research of interest to physical chemists, biophysical chemists, chemical physicists, physicists, material scientists, and engineers. An important criterion for acceptance is that the paper reports a significant scientific advance and/or physical insight such that rapid publication is essential. Two issues of JPC Letters are published each month.