用于OBOC小分子库的编码方法,使用二相方法进行编码标签的梯级合成
Xiaobing Wang1, Jinhua Zhang, Aimin Song
1Division of Hematology and Oncology, Department of Internal Medicine, UC Davis Medical Center, 4501 X Street, Sacramento, California 95817, USA.
Journal of the American Chemical Society
|May 6, 2004
概括
一个新的编码策略用于一个珠子一个化合物 (OBOC) 库使用双层珠子与内部编码标签. 这种方法可以明确识别小分子,促进药物发现和化学生物学.
科学领域:
- 化学生物学 化学生物学
- 组合化学 组合化学
- 药物发现 药物发现 药物发现
背景情况:
- 一颗珠一颗化合物 (OBOC) 组合库使大量化合物的快速合成和选成为可能.
- 正确的正复合珠的解码对于利用 OBOC 库的潜力至关重要.
- 现有的编码方法需要在高通量应用中进行改进.
研究的目的:
- 为OBOC小分子库开发一种新,强大和高通量编码策略.
- 允许从正珠中明确的结构识别化合物.
- 提高OBOC图书馆选和分析的效率.
主要方法:
- 开发一种双层珠子系统,将表面显示的化合物与内部可切割的编码标签相结合.
- 使用阶梯合成方法和在珠子内部的化学编码.
- 将融入可切割的链接器中,以产生用于质谱分析 (MALDI-TOF-MS) 的特征同位素指纹.
- 采用双相合成方法对功能进行拓分离.
主要成果:
- 通过使用新型编码策略,成功合成和验证了12288个成员的OBOC小分子库.
- 在对斯特雷普塔维丁进行查后,在阳性珠上的化合物的化学结构的明确确定.
- 证明MALDI-TOF-MS光谱中的相邻峰之间的质量差异允许结构阐明.
- 编码策略还为表面显示化合物的质量提供了洞察力.
结论:
- 开发的编码策略为解码OBOC组合库提供了一个强大的工具.
- 这种方法显著提高了识别活性化合物的能力,加速了药物发现.
- 含的链接器简化了质谱解释,并证实了化合物的完整性.
相关概念视频
02:27DNA Base Pairing
Erwin Chargaff’s rules on DNA equivalence paved the way for the discovery of base pairing in DNA. Chargaff’s rules state that in a double-stranded DNA molecule,
02:27DNA Base Pairing
Erwin Chargaff’s rules on DNA equivalence paved the way for the discovery of base pairing in DNA. Chargaff’s rules state that in a double-stranded DNA molecule,
03:31Labeling DNA Probes
DNA probes are fragments of DNA labeled with a reporter tag to enable their detection or purification. The resulting labeled DNA probes can then hybridize to target nucleic acid sequences through complementary base-pairing, and may be used to recover or identify these regions.
Radioisotopes, fluorophores, or small molecule binding partners like biotin or digoxigenin, are the most widely used reporter tags for labeling DNA probes. These labels can be attached to the probe DNA molecule via...
Radioisotopes, fluorophores, or small molecule binding partners like biotin or digoxigenin, are the most widely used reporter tags for labeling DNA probes. These labels can be attached to the probe DNA molecule via...
00:55Ordinal Level of Measurement
The way a set of data is measured is called its level of measurement. Correct statistical procedures depend on a researcher being familiar with levels of measurement. For analysis, data are classified into four levels of measurement—nominal, ordinal, interval, and ratio.
Data measured using an ordinal scale are similar to nominal scale data, but there is one major difference. The ordinal scale data can be ordered. An example of ordinal scale data is a list of the top five national parks in the...
Data measured using an ordinal scale are similar to nominal scale data, but there is one major difference. The ordinal scale data can be ordered. An example of ordinal scale data is a list of the top five national parks in the...
01:21Bulk Modulus
The bulk modulus is a scientific term used to describe a material's resistance to uniform compression. It is the proportionality constant that links a change in pressure to the resulting relative volume change.
01:19Encoding
Information enters the brain through encoding, which is the input of information into the memory system. Once sensory information is received from the environment, the brain labels or codes it. The information is then organized with similar information and connected to existing concepts. Encoding occurs through automatic processing and effortful processing.
Automatic processing involves the encoding of details like time, space, frequency, and the meaning of words, usually done without conscious...
Automatic processing involves the encoding of details like time, space, frequency, and the meaning of words, usually done without conscious...