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Exploring the Nucleobase-Specific Hydrophobic Interaction of Cryptolepine Hydrate with RNA and Its Subsequent Sequestration
Langmuir ( IF 3.7 ) Pub Date : 2021-09-09 , DOI: 10.1021/acs.langmuir.1c02123 Atanu Nandy 1 , Shashi Shekhar 1 , Bijan K Paul 2 , Saptarshi Mukherjee 1
Langmuir ( IF 3.7 ) Pub Date : 2021-09-09 , DOI: 10.1021/acs.langmuir.1c02123 Atanu Nandy 1 , Shashi Shekhar 1 , Bijan K Paul 2 , Saptarshi Mukherjee 1
Affiliation
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The study of the interactions of drug molecules with genetic materials plays a key role underlying the development of new drugs for many life-threatening diseases in pharmaceutical industries. Understanding their fundamental base-specific and/or groove-binding interaction is crucial to target the genetic material with an external drug, which can pave the way to curing diseases related to the genetic material. Here, we studied the interaction of cryptolepine hydrate (CRYP) with RNA under physiological conditions knowing the antimalarial and anticancer activities of the drug. Our experiments explicitly demonstrate that CRYP interacts with the guanine- and adenine-rich region within the RNA duplex. The pivotal role of the hydrophobic interaction governing the interaction is substantiated by temperature-dependent isothermal titration calorimetry experiments and spectroscopic studies. Circular dichroism study underpins a principally intercalative mode of binding of CRYP with RNA. This interaction is found to be drastically affected in the presence of magnesium salt, which has a strong propensity to coordinate with RNA nucleobases, which can in turn modulate the interaction of the drug with RNA. The temperature-dependent calorimetric results substantiate the occurrence of entropy–enthalpy compensation, which enabled us to rule out the possibility of groove binding of the drug with RNA. Furthermore, our results also show the application of host–guest chemistry in sequestering the RNA-bound drug, which is crucial to the development of safer therapeutic applications.
中文翻译：
探索 Cryptolepine Hydrate 与 RNA 的核碱基特异性疏水相互作用及其后续螯合
药物分子与遗传物质相互作用的研究在制药工业中许多危及生命的疾病的新药开发中起着关键作用。了解它们的基本碱基特异性和/或沟结合相互作用对于用外部药物靶向遗传物质至关重要，这可以为治疗与遗传物质相关的疾病铺平道路。在这里，我们研究了水合隐甘平 (CRYP) 在生理条件下与 RNA 的相互作用，了解该药物的抗疟和抗癌活性。我们的实验明确表明 CRYP 与 RNA 双链体内富含鸟嘌呤和腺嘌呤的区域相互作用。依赖于温度的等温滴定量热实验和光谱研究证实了疏水相互作用控制相互作用的关键作用。圆二色性研究支持 CRYP 与 RNA 结合的主要嵌入模式。发现这种相互作用在镁盐的存在下会受到极大的影响，镁盐具有很强的与 RNA 核碱基协调的倾向，这反过来又可以调节药物与 RNA 的相互作用。温度相关的量热结果证实了熵-焓补偿的发生，这使我们能够排除药物与 RNA 凹槽结合的可能性。此外，我们的结果还显示了宿主 - 客体化学在螯合 RNA 结合药物中的应用，
更新日期：2021-09-21
中文翻译：
探索 Cryptolepine Hydrate 与 RNA 的核碱基特异性疏水相互作用及其后续螯合
药物分子与遗传物质相互作用的研究在制药工业中许多危及生命的疾病的新药开发中起着关键作用。了解它们的基本碱基特异性和/或沟结合相互作用对于用外部药物靶向遗传物质至关重要，这可以为治疗与遗传物质相关的疾病铺平道路。在这里，我们研究了水合隐甘平 (CRYP) 在生理条件下与 RNA 的相互作用，了解该药物的抗疟和抗癌活性。我们的实验明确表明 CRYP 与 RNA 双链体内富含鸟嘌呤和腺嘌呤的区域相互作用。依赖于温度的等温滴定量热实验和光谱研究证实了疏水相互作用控制相互作用的关键作用。圆二色性研究支持 CRYP 与 RNA 结合的主要嵌入模式。发现这种相互作用在镁盐的存在下会受到极大的影响，镁盐具有很强的与 RNA 核碱基协调的倾向，这反过来又可以调节药物与 RNA 的相互作用。温度相关的量热结果证实了熵-焓补偿的发生，这使我们能够排除药物与 RNA 凹槽结合的可能性。此外，我们的结果还显示了宿主 - 客体化学在螯合 RNA 结合药物中的应用，
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