Efficient Pictet–Spengler Bioconjugation with N‐Substituted Pyrrolyl Alanine Derivatives

S Pomplun, MYH Mohamed, T Oelschlaegel… - Angewandte …, 2019 - Wiley Online Library
S Pomplun, MYH Mohamed, T Oelschlaegel, C Wellner, F Bergmann
Angewandte Chemie, 2019Wiley Online Library
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 …
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.
Wiley Online Library
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