Dąbrowska Aleksandra M, Kaźmierkiewicz Rajmund, Barabaś-Lepak Anna M, Biedulska Małgorzata, Chylewska Agnieszka
Intermolecular Interaction Laboratory, Department of Bioinorganic Chemistry, Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308 Gdańsk, Poland.
Laboratory of Biomolecular Systems Simulations, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Abrahama 58, 80-307 Gdańsk, Poland.
J Phys Chem B. 2025 Jan 23;129(3):911-929. doi: 10.1021/acs.jpcb.4c08136. Epub 2025 Jan 14.
This study extends previous research, particularly focusing on patented scientific objects No. ID: PL 240 353 B1, investigating the physicochemical properties of the methyl 3-azido- and 3-amino-2,3-dideoxysaccharides with a nucleoside scaffold similar to 3'-azidothymidine (AZT). The study utilizes multiwavelength spectrophotometric and potentiometric methods to evaluate the ionization of the saccharide units in aqueous solutions. p values, obtained from two independent methods, reveal significant sugar ionization effects on UV spectra with varying pH levels. Stability constants for divalent metal ion complexes (Cu and Ni) with the saccharide isomers indicate that complex stoichiometries and stabilities are highly dependent on the configuration of sugar ring substituents. Spectrophotometric results show a descending order of -DNA-binding affinity: > > > , suggesting varied interaction strengths. Molecular docking of models of synthesized -glycosides confirmed their potential as reverse transcriptase inhibitors. Among the derivatives tested, the compound displays the highest interaction with the enzyme active site residues and DNA, suggesting it may possess the greatest efficacy. Our reported results highlight the promising inhibitory properties of novel -glycosides against HIV reverse transcriptase, supporting their potential development as antiviral agents.
本研究扩展了先前的研究，特别聚焦于专利科学对象编号为PL 240 353 B1的研究，该研究调查了具有类似于3'-叠氮胸苷（AZT）的核苷支架的3-叠氮基-和3-氨基-2,3-二脱氧甲基糖的物理化学性质。该研究利用多波长分光光度法和电位分析法来评估糖单元在水溶液中的电离情况。通过两种独立方法获得的p值显示，在不同pH水平下，糖的电离对紫外光谱有显著影响。二价金属离子（铜和镍）与糖异构体的络合稳定常数表明，络合化学计量和稳定性高度依赖于糖环取代基的构型。分光光度法结果显示，与DNA结合亲和力的降序为：> > > ，表明相互作用强度各不相同。合成糖苷模型的分子对接证实了它们作为逆转录酶抑制剂的潜力。在所测试的衍生物中，化合物与酶活性位点残基和DNA的相互作用最强，表明它可能具有最大的功效。我们报告的结果突出了新型糖苷对HIV逆转录酶的有前景的抑制特性，支持它们作为抗病毒药物的潜在开发。
