作为蛋白质氨酸甲基转移酶SETD2的抑制剂和结构探针的synefungin衍生物
Weihong Zheng1, Glorymar Ibáñez, Hong Wu
1Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
Journal of the American Chemical Society
|October 10, 2012
概括
研究人员使用特权小分子支架确定了蛋白质氨基甲基转移酶 (PKMTs) 的特定抑制剂. N-propyl sinefungin选择性地准SETD2,揭示了其调节作用,并为甲基转移酶研究提供了一个探针.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 表观遗传调节在生理和病理过程中至关重要.
- 超过50个人类蛋白质氨酸甲基转移酶 (PKMTs) 是关键的表观遗传调节者.
- 需要针对特定目标的PKMT抑制剂来研究单个PKMT功能.
研究的目的:
- 开发一种方法来识别特定标的甲基转移酶抑制剂.
- 选特权的小分子支架对各种甲基转移酶进行选.
- 为了确定SETD2甲基转移酶的抑制剂.
主要方法:
- 对特权的小分子支架进行对甲基转移酶的选.
- 鉴定N-propyl sinefungin (Pr-SNF) 作为一个SETD2抑制剂.
- 使用Pr-SNF作为结构探针来研究SETD2的催化机制和基质访问.
主要成果:
- 证明了选PKMT抑制剂的特权支架的可行性.
- 确定了N-propyl sinefungin (Pr-SNF) 作为SETD2.2的选择性抑制剂.
- 通过拓重新配置阐明了SETD2在基板访问调节中的后SET循环的双重作用.
结论:
- 优势的赛因芬根基架可以有效地用于发现特定标的甲基转移酶抑制剂.
- N-propyl sinefungin 作为一种有价值的化学探针,用于研究 SETD2.
- 这些发现为SETD2的监管机制及其作为治疗点的潜力提供了洞察力.
相关概念视频
01:15Antifungal Agents
Amphotericin B is a broad-spectrum antifungal agent that exploits structural differences between fungal and mammalian cell membranes. Its amphipathic structure—featuring a hydrophobic polyene-lactone ring and a hydrophilic region containing mycosamine and carboxylic acid groups—enables selective binding to ergosterol, a sterol predominantly found in fungal plasma membranes. This selective interaction underlies the drug’s antifungal activity, although weak binding to cholesterol contributes to...
02:04Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.