Building photoswitchable 3,4'-AMPB peptides: Probing chemical ligation methods with reducible azobenzene thioesters

Photoswitchable peptides were synthesized by using cysteine- and auxiliary-based native chemical ligation reactions. For this purpose, the two regioisomeric azobenzene building blocks 3,4'-AMPB thioester 1b and 4,4'-AMPB thioester 2b were employed in the ligation reactions. While 4,4'-AMPB requires the 4,5,6-trimethoxy-2-mercaptobenzyl auxiliary to minimize reduction of the diazene unit, 3,4'-AMPB can be used in combination with the 4,5,6-trimethoxy-2-mercaptobenzyl auxiliary as well as the Nα-2-mercaptoethyl auxiliary. Thus, 3,4'-AMPB derivatives/peptides proved to be significantly less prone to reduction by aliphatic and aromatic thiols than were the 4,4'-AMPB compounds.