Efficient Pictet–Spengler Bioconjugation with N‐Substituted Pyrrolyl Alanine Derivatives. Issue 11 (7th February 2019)

• Record Type: Journal Article
• Authors: Pomplun, Sebastian; Mohamed, Mohamed Y. H.; Oelschlaegel, Tobias; Wellner, Christian; Bergmann, Frank
• Is Part Of: Angewandte Chemie international edition. Volume 58:Issue 11(2019)
• Page Start: 3542
• Page End: 3547
• Publication Date: 2019-02-07
• Subjects: aldehydes -- antibody conjugation -- oligonucleotide modification -- Pictet–Spengler -- protein modification; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201814200
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: 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. Abstract : Small but mighty : The atom efficient and easy to synthesize reagent N ‐pyrrolyl alanine is shown to undergo fast and site‐selective Pictet–Spengler bioconjugation. This catalyst‐free conjugation strategy was successfully applied for the biocompatible, site‐specific, and stable labeling of aldehydes in peptides, antibodies and, nucleic acids.