用于mRNA显示的铁酶催化宏循环
Matthew C Fleming1,2, Matthew M Bowler1,2, Rodney Park3
1Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, 301 Pharmacy Lane, Chapel Hill, North Carolina 27599, United States.
Journal of the American Chemical Society
|May 8, 2023
概括
我们开发了一种新方法, 这项技术成功地发现了向黑色素相关抗原A4 (MAGE-A4) 的强有力的配体.
科学领域:
- 生物化学
- 分子生物学
- 医学化学
背景情况:
- 传递 RNA (mRNA) 显示是一种用于发现高亲和性联体的强大方法.
- 有限的循环化化学成分与mRNA显示相容,限制了宏环的发现.
- 氨酸酶催化氧化氨酸到一个有反应性的o氨酸.
研究的目的:
- 介绍和描述一种与mRNA显示相容的新型铁酶介导循环.
- 应用这种方法来发现向黑色素相关抗原A4 (MAGE-A4) 的宏循环配体.
主要方法:
- 含有氨酸和氨酸残留物的酸被用氨酸酶进行循环处理.
- 铁酶介导的循环化以其适用于各种宏观循环大小和支架的特性.
- 开发的方法与mRNA显示相结合,用于选MAGE- A4向配体.
主要成果:
- 酸酶治疗 含氨酸和氨酸的快速循环.
- 循环化方法在不同宏观循环大小和支架上被证明是多功能性的.
- 发现的宏环联体强烈抑制了纳米IC50值的MAGE- A4结合轴.
- 宏循环连接剂比非循环类同类具有显著优势,IC50值降低了约40倍.
结论:
- 铁酶介导的循环化是一种广泛适用的和有效的产生宏环的方法.
- 将铁酶循环与mRNA显示结合起来是有效的发现强大的宏循环配体.
- 发现的向MAGE- A4的宏循环配体显示出治疗黑色素瘤的潜力.
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