Development of New Bioorthogonal Reactions Based on Rational Computational Design

生物正交化学使生物大分子的原位修饰成为可能，开辟了研究细胞过程而不破坏活生物体的途径。这个跨学科的项目结合理论、合成和机理研究工作来开发新的生物正交反应。它将导致一套新的试剂设计用于以后的生物学研究的发展。生物正交反应在体内应用的一个主要障碍是在生物亲核试剂存在的情况下，所采用的反应伙伴的鲁棒性有限。在这个项目中，我们的目标是发现一种计算和光谱方法的结合，以预测生物正交反应中常用的试剂的稳定性。我们将特别关注可见光诱导的生物正交反应的发展，因为目前在这一领域还没有太大的进展，这类反应对生物大分子的选择性标记具有极大的兴趣。

Bioorthogonal chemistry makes in situ modification of biomacromolecules possible, opening avenues to study cellular processes without disruption of the living organisms. This interdisciplinary project combines theoretical, synthetic and mechanistic research work to develop new bioorthogonal reactions. It will result in the development of a new set of reagents designed for use in later biological studies. A major obstacle of in vivo applications of bioorthogonal reactions is the limited robustness of the employed reaction partners in the presence of biogenic nucleophiles. In this project, we aim to discover a combination of computational and spectroscopic methods to predict the stability of the reagents that are commonly used in bioorthogonal reactions. Special attention will be given to the development of visible light-induced bioorthogonal reactions, as not much progress was made in this field so far, and such reactions are of utmost interest for the selective labeling of biomacromolecules.