Furyl-Alanine: A Novel Photo-Click Amino Acid

Labeling with different tags and reporter groups is a pivotal technique for the elucidation of peptide and protein function. A novel and innovative approach is the site-specific labeling using the unnatural amino acid 2-furyl-alanine. UV-irradiation in the presence of oxygen and a photosensitizer converts furyl-alanine to an unsaturated dicarbonyl compound. This intermediate selectively reacts with certain nucleophiles such as hydrazine derivatives of dyes or fluorescent labels. This reaction can be used for the site-specific labeling of peptides and proteins and can be carried out in aqueous solution.

2-Furyl-alanine can be incorporated into peptides either via SPPS or by using enzymatic approaches. Iris Biotech offers Fmoc-L-Ala(2-Furyl)-OH suitable for SPPS, as well as H-L-Ala(2-Furyl)-OH which can be incorporated into proteins using amber suppression methodology.

References:

• Novel furan-oxidation based site-specific conjugation methodology for peptide labeling and antibody drug conjugates; presented at the 6th World ADC meeting October 19th-22nd 2015, San Diego, CA; An Van Den Bulcke, Eirini Antonatou, Willem Vannecke, Kurt Hoogewijs and Annemieke Madder
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• Sequence Specific DNA Cross-Linking Triggered by Visible Light; M. Op de Beeck and A. Madder; Journal of the American Chemical Society 2012; 134: 10737-10740. doi:10.1021/ja301901p
• Unprecedented C-Selective Interstrand Cross-Linking through in Situ Oxidation of Furan-Modified Oligodeoxynucleotides; M. Op de Beeck and A. Madder; Journal of the American Chemical Society 2011; 133: 796-807. doi:10.1021/ja1048169
• Furan-modified oligonucleotides for fast, high-yielding and site-selective DNA inter-strand cross-linking with non-modified complements; K. Stevens and A. Madder; Nucleic acids research 2009; 37: 1555-1565. doi:10.1093/nar/gkn1077
• From DNA cross-linking to peptide labeling: on the versatility of the furan-oxidation-conjugation strategy; A. Deceuninck and A. Madder; Chemical Communications 2009: 340-342. doi:10.1039/b817447d
• Bioorthogonal Chemistry: Fishing for Selectivity in a Sea of Functionality; E. M. Sletten and C. R. Bertozzi; Angewandte Chemie International Edition 2009; 48: 6974-6998. doi:10.1002/anie.200900942
• Structural Basis of Furan–Amino Acid Recognition by a Polyspecific Aminoacyl-tRNA-Synthetase and its Genetic Encoding in Human Cells; M. J. Schmidt, A. Weber, M. Pott, W. Welte and D. Summerer; Chembiochem : a European journal of chemical biology 2014; 15: 1755-1760. doi:10.1002/cbic.201402006
• Red-Light-Controlled Protein–RNA Crosslinking with a Genetically Encoded Furan; M. J. Schmidt and D. Summerer; Angewandte Chemie International Edition 2013; 52: 4690-4693. doi:10.1002/anie.201300754