可编程的化学进化与自然/非自然构建块.
Ping Liu1, Refeya Jannatul2, Juan Chen1
1Department of Nutrition and Health, China Agricultural University, 100091, Beijing, China.
Angewandte Chemie (International ed. in English)
|July 29, 2024
概括
可编程化学进化 (PCEvo) 快速生成使用各种非自然构建块的高亲和度结合剂. 这种方法通过探索广的化学空间,为新型分子识别剂加速药物发现.
科学领域:
- 药用化学 医学化学
- 化学生物学 化学生物学
- 药物发现 药物发现 药物发现
背景情况:
- 非自然构建块 (BBs) 为分子识别和药物发现提供了广泛的化学多样性.
- 目前的实验室进化系统面临的挑战是有效地产生具有众多多样化的BB的生物活性分子.
研究的目的:
- 引入可编程化学进化 (PCEvo) 以克服当前实验室进化系统的局限性.
- 能够快速生成高亲和度结合剂,使用大量多样化的非自然BBs.
主要方法:
- 整合化学信息分类与高通量阵列合成和选.
- 构建多样化的组合图书馆,以创建进化的祖先分子.
- 使用PCEvo带有108个BB,探索超过1017个化学空间.
主要成果:
- 识别对抗SAR-CoV-2 RBD和Claudin18.2目标的双循环皮多米米特结合剂,具有纳米分子亲和力.
- 在2-4个周期内实现加速分子进化.
- 克劳丁18.2结合剂可以选择性地染色胃腺癌细胞系和患者样本.
结论:
- PCEvo显著推进了非自然BBs的利用,用于快速化学进化.
- 这种方法适用于具有或没有先前结构信息或连接物偏好的目标.
- PCEvo加速了用于治疗应用的新生物活性分子的发现.
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