Rapid Photolysis‐Mediated Folding of Disulfide‐Rich Peptides

• Published in: Chemistry : a European journal Vol. 25; no. 36; pp. 8599 - 8603
• Main Authors: Patil, Nitin A., Karas, John A., Wade, John D., Hossain, Mohammed Akhter, Tailhades, Julien
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 26.06.2019; Wiley Subscription Services, Inc
• Subjects: Chemistry; Chemistry, Multidisciplinary; Conotoxins - chemistry; Conotoxins - metabolism; disulfides; Disulfides - chemistry; Drug development; Humans; Insulin; Insulin - chemistry; Insulin - metabolism; Organic chemistry; Oxidation-Reduction; Peptides; Peptides - chemistry; Peptides - metabolism; Photolysis; Physical Sciences; protein engineering; Protein Folding; Science & Technology; Stereoisomerism; Structure-Activity Relationship; structure–activity relationships; Ultraviolet Rays; ANALOGS; photolysis; REGIOSELECTIVE FORMATION; LIGATION; peptides; HUMAN INSULIN; BOND FORMATION; CONOPEPTIDES; disulfides; protein engineering; structure-activity relationships; CHEMISTRY; protein folding; CHEMICAL-SYNTHESIS; PROTECTING GROUPS; ACYL-TRANSFER
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201901334

Structure–activity relationship studies are a highly time‐consuming aspect of peptide‐based drug development, particularly in the assembly of disulfide‐rich peptides, which often requires multiple synthetic steps and purifications. Therefore, it is vital to develop rapid and efficient chemical methods to readily access the desired peptides. We have developed a photolysis‐mediated “one‐pot” strategy for regioselective disulfide bond formation. The new pairing system utilises two ortho‐nitroveratryl protected cysteines to generate two disulfide bridges in less than one hour in good yield. This strategy was applied to the synthesis of complex disulfide‐rich peptides such as Rho‐conotoxin ρ‐TIA and native human insulin. Controlled folding: A photolysis‐mediated “one‐pot” strategy for regioselective disulfide bond formation in peptides has been developed (see figure). This strategy was applied to the synthesis of complex disulfide‐rich peptides such as Rho‐conotoxin ρ‐TIA and native human insulin.