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In Silico Selection and Validation of High-Affinity ssDNA Aptamers Targeting Paromomycin
Analytical Chemistry ( IF 6.7 ) Pub Date : 2023-06-29 , DOI: 10.1021/acs.analchem.3c01575 Jiaqing Li 1, 2 , Yangyang Liu 3 , Dongdong Liu 1 , Tong Xu 1, 2 , Chen Zhang 1 , Jianjun Li 1 , Zhuo A Wang 1 , Yuguang Du 1
Analytical Chemistry ( IF 6.7 ) Pub Date : 2023-06-29 , DOI: 10.1021/acs.analchem.3c01575 Jiaqing Li 1, 2 , Yangyang Liu 3 , Dongdong Liu 1 , Tong Xu 1, 2 , Chen Zhang 1 , Jianjun Li 1 , Zhuo A Wang 1 , Yuguang Du 1
Affiliation
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Glycans are promising for disease diagnosis since glycan biosynthesis is significantly affected by disease states, and glycosylation changes are probably more pronounced than protein expression during the transformation to the diseased condition. Glycan-specific aptamers can be developed for challenging applications such as cancer targeting; however, the high flexibility of glycosidic bonds and scarcity of studies on glycan–aptamer binding mechanisms increased the difficulty of screening. In this work, the model of interactions between glycans and ssDNA aptamers synthesized based on the sequence of rRNA genes was developed. Our simulation-based approach revealed that paromomycin as a representative example of glycans is preferred to bind base-restricted stem structures of aptamers because they are more critical in stabilizing the flexible structures of glycans. Combined experiments and simulations have identified two optimal mutant aptamers. Our work would provide a potential strategy that the glycan-binding rRNA genes could act as the initial aptamer pools to accelerate aptamer screening. In addition, this in silico workflow would be potentially applied in the more extensive in vitro development and application of RNA-templated ssDNA aptamers targeting glycans.
中文翻译：
靶向巴龙霉素的高亲和力 ssDNA 适体的计算机模拟选择和验证
聚糖在疾病诊断方面很有前景，因为聚糖生物合成受到疾病状态的显着影响，并且在向疾病状态转变期间，糖基化变化可能比蛋白质表达更明显。可以开发聚糖特异性适体用于具有挑战性的应用，例如癌症靶向；然而，糖苷键的高度灵活性以及聚糖-适体结合机制研究的缺乏增加了筛选的难度。在这项工作中，开发了基于 rRNA 基因序列合成的聚糖和 ssDNA 适体之间相互作用的模型。我们基于模拟的方法表明，巴龙霉素作为聚糖的代表性例子，更适合结合适体的碱基限制茎结构，因为它们对于稳定聚糖的柔性结构更为关键。结合实验和模拟已经确定了两种最佳的突变适体。我们的工作将提供一种潜在的策略，即聚糖结合 rRNA 基因可以作为初始适体池来加速适体筛选。此外，这计算机工作流程将有可能应用于更广泛的针对聚糖的 RNA 模板 ssDNA 适体的体外开发和应用。
更新日期：2023-06-29
中文翻译：
靶向巴龙霉素的高亲和力 ssDNA 适体的计算机模拟选择和验证
聚糖在疾病诊断方面很有前景，因为聚糖生物合成受到疾病状态的显着影响，并且在向疾病状态转变期间，糖基化变化可能比蛋白质表达更明显。可以开发聚糖特异性适体用于具有挑战性的应用，例如癌症靶向；然而，糖苷键的高度灵活性以及聚糖-适体结合机制研究的缺乏增加了筛选的难度。在这项工作中，开发了基于 rRNA 基因序列合成的聚糖和 ssDNA 适体之间相互作用的模型。我们基于模拟的方法表明，巴龙霉素作为聚糖的代表性例子，更适合结合适体的碱基限制茎结构，因为它们对于稳定聚糖的柔性结构更为关键。结合实验和模拟已经确定了两种最佳的突变适体。我们的工作将提供一种潜在的策略，即聚糖结合 rRNA 基因可以作为初始适体池来加速适体筛选。此外，这计算机工作流程将有可能应用于更广泛的针对聚糖的 RNA 模板 ssDNA 适体的体外开发和应用。
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