Laser‐Initiated Radical Trifluoromethylation of Peptides and Proteins: Application to Mass‐Spectrometry‐Based Protein Footprinting

• Published in: Angewandte Chemie International Edition Vol. 56; no. 45; pp. 14007 - 14010
• Main Authors: Cheng, Ming, Zhang, Bojie, Cui, Weidong, Gross, Michael L.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 06.11.2017
• Edition: International ed. in English
• Subjects: Amino acids; Amino Acids - chemistry; Biomedical materials; Biotechnology; Fluorine Compounds - chemistry; Footprinting; Lasers; mass spectrometry; Mass Spectrometry - methods; Membrane proteins; Methylation; Myoglobins; Organic chemistry; Peptides; Peptides - chemistry; Protein Binding; Protein Conformation; Protein Folding; Proteins; Proteins - chemistry; radical reactions; reaction mechanisms; Solvents - chemistry; Spectrometry; Surgical implants; radical reactions; reaction mechanisms; mass spectrometry; membrane proteins; amino acids
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201706697

Described is a novel, laser‐initiated radical trifluoromethylation for protein footprinting and its broad residue coverage. .CF3 reacts with 18 of the 20 common amino acids, including Gly, Ala, Ser, Thr, Asp, and Glu, which are relatively silent with regard to .OH. This new approach to footprinting is a bridge between trifluoromethylation in materials and medicinal chemistry and structural biology and biotechnology. Its application to a membrane protein and to myoglobin show that the approach is sensitive to protein conformational change and solvent accessibility. Footprints: Reported is a novel, laser‐initiated trifluoromethylation method for protein footprinting. The trifluoromethyl radical reacts with 18 of the 20 common amino acids. It can probe the conformational changes and the solvent accessibility of proteins, thus serving as a footprinting agent with high hydrophobicity. MS=mass spectrometry.