Exploring and Exploiting Polar鈭捪€ Interactions with Fluorinated Aromatic Amino Acids
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- 作者：Christopher J. Pace ; Jianmin Gao
- 刊名：Accounts of Chemical Research
- 出版年：2013
- 出版时间：April 16, 2013
- 年：2013
- 卷：46
- 期：4
- 页码：907-915
- 全文大小：549K
- 年卷期：v.46,no.4(April 16, 2013)
- ISSN：1520-4898
文摘
Fluorination has become an increasingly attrac-tive strategy in protein engineering for both basic research and biomedical applications. Thus researchers would like to understand the consequences of fluorination to the structure, stability, and function of target proteins. Although a substantial amount of work has focused on understanding the properties of fluorinated aliphatic amino acids, much less is known about fluorinated aromatic residues. In addition, polar鈭捪€ interactions, often referred to as aromatic interactions, may play a significant role in protein folding and protein鈥損rotein interactions. Fluorination of aromatic residues presents an ideal strategy for probing polar鈭捪€ interactions in proteins.
This Account summarizes the recent studies of the incorporation of fluorinated aromatic amino acids into proteins. Herein we discuss the effects of fluorinating aromatic residues and rationalize them in the context of polar鈭捪€ interactions. The results strongly support the proposal that polar鈭捪€ interactions are energetically significant to protein folding and function. For example, an edge鈥揻ace interaction of a pair of phenylalanines contributes as much as 鈭? kcal/mol to protein stability, while cation鈭捪€ interactions can be much stronger. Furthermore, this new knowledge provides guidelines for protein engineering with fluorination. Importantly, incorporating perfluorinated aromatic residues into proteins enables novel mechanisms of molecular recognition that do not exist in native proteins, such as arene-perfluoroarene stacking. Such novel mechanisms can be used for programming protein folding specificity and engineering peptide-based materials.
This Account summarizes the recent studies of the incorporation of fluorinated aromatic amino acids into proteins. Herein we discuss the effects of fluorinating aromatic residues and rationalize them in the context of polar鈭捪€ interactions. The results strongly support the proposal that polar鈭捪€ interactions are energetically significant to protein folding and function. For example, an edge鈥揻ace interaction of a pair of phenylalanines contributes as much as 鈭? kcal/mol to protein stability, while cation鈭捪€ interactions can be much stronger. Furthermore, this new knowledge provides guidelines for protein engineering with fluorination. Importantly, incorporating perfluorinated aromatic residues into proteins enables novel mechanisms of molecular recognition that do not exist in native proteins, such as arene-perfluoroarene stacking. Such novel mechanisms can be used for programming protein folding specificity and engineering peptide-based materials.