Efficient Pictet-Spengler Bioconjugation with N-Substituted Pyrrolyl Alanine Derivatives.
Efficient Pictet-Spengler Bioconjugation with N-Substituted Pyrrolyl Alanine Derivatives.
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DOI：
10.1002/anie.201814200
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发表时间：
2019-02
影响因子：
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通讯作者：
S. Pomplun;M. Mohamed;Tobias Oelschlaegel;Christian Wellner;F. Bergmann
中科院分区：
文献类型：
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作者：
S. Pomplun;M. Mohamed;Tobias Oelschlaegel;Christian Wellner;F. Bergmann
我们发现n -吡咯酰丙氨酸衍生物是与含醛生物分子进行快速选择性Pictet-Spengler反应的有效试剂。迄今为止描述的其他醛标记方法有几个缺点，如水解不稳定，反应动力学缓慢或不易获得标记试剂。吡咯- 2-乙胺在吡咯氮上取代的Pictet-Spengler环化反应明显快于在α-和β-位置取代的类似物。功能化n -吡咯基丙氨酸衍生物可以在2-3步内从市售材料合成。该试剂体积小，反应速率高，易于合成，使得吡咯酰丙氨酸Pictet-Spengler （PAPS）成为生物偶联反应的理想选择。PAPS被证明是抗体位点选择性生物素化以及核酸衍生物缩合的有效策略，证明了该试剂的多功能性。
We discovered N-pyrrolyl alanine derivatives as efficient reagents for the fast and selective Pictet-Spengler reaction with aldehyde-containing biomolecules. Other aldehyde-labeling methods described so far have several drawbacks, like hydrolytic instability, slow reaction kinetics or not readily available labeling reagents. Pictet-Spengler cyclizations of pyrrolyl 2-ethylamine substituted at the pyrrole nitrogen are significantly faster than with analogues substituted at the α- and β- position. Functionalized N-pyrrolyl alanine derivatives can be synthesized in only 2-3 steps from commercially available materials. The small size of the reagent, the high reaction rate, and the easy synthesis make pyrrolyl alanine Pictet-Spengler (PAPS) an attractive choice for bioconjugation reactions. PAPS was shown as an efficient strategy for the site-selective biotinylation of an antibody as well as for the condensation of nucleic-acid derivatives, demonstrating the versatility of this reagent.