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对L1细胞粘附分子DNA适应体的结构优化和相互作用研究

Zhenhao Long^1,2, Tao Bing^1,3, Xiangru Zhang^1,2

¹Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, CAS Research and Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.

International journal of molecular sciences

|May 27, 2023

概括

研究人员优化了DNA吸附体,以强烈结合L1细胞粘附分子 (L1CAM). 这些增强的胺体为L1CAM研究和检测提供了改进的工具,有助于药物开发.

科学领域:

生物化学生物化学
分子生物学分子生物学
生物技术是生物技术.

背景情况:

L1细胞粘附分子 (L1CAM) 对于神经系统发育至关重要,并与瘤进展有关.
开发针对L1CAM的特定配体对于生物医学研究和诊断应用至关重要.

研究的目的:

为了优化DNA吸附体,以增强对L1CAM的结合亲和力.
阐明阿普坦和L1CAM之间的分子相互作用机制.
为开发针对L1CAM的药物和检测探针提供指导.

主要方法:

用序列突变和扩展来优化DNA的aptamer yly12对L1CAM.
结合亲和力在室温和37°C下进行评估.
结构分析揭示了aptamer的二次结构和关键的结合区域.
证实了对L1CAM的aptamers的域特定结合.

主要成果:

优化的阿普坦 (yly20, yly21) 对L1CAM具有10-24倍强的结合亲和力.
阿普塔默采用了针头结构,其中的关键核酸位于循环I和相邻区域.
鉴定出I茎对稳定阿普坦-L1CAM结合结构至关重要.
伊利系列的阿普坦酶特别与L1CAM的Ig6域结合.

结论:

经过优化后的DNA吸收体显著增强了对L1CAM的结合.
这项研究提供了对阿普坦-L1CAM相互作用的详细分子理解.
这些发现有助于设计基于L1CAM的新型诊断和治疗方法.

关键词:

一个L1CAM.一个aptamer的应用程序.具有约束力的机制.分子识别分子识别序列优化优化序列优化

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