Defying Entropy: Forming Large Head-to-Tail Macrocycles in the Gas Phase

摘要

In solution, the synthesis of head-to-tail macrocyclic peptides is notoriously challenging for smaller peptides due to trans amide bonds, and synthetic strategies frequently involve the insertion of proline or D-amino acids. Conversely, cycliza-tion of larger peptides is often straightforward, provided that competing reactions can be minimized. In recent years, it was discovered that macrocyclic peptides can also be formed in the gas phase, during the fragmentation chemistry of nrotonated peptides inside mass spectrometers.