Constructing Thioether/Vinyl Sulfide-tethered Helical Peptides Via Photo-induced Thiol-ene/yne Hydrothiolation

These methods simplify the generation of thioether-tethered cyclic peptides due to the use of the thio-ene or thio-yne click chemistry that possesses superior functional group tolerance and good yield. The main advantage of this technique is that a thioether tether provides a traceless modification site, which significantly expand the chemical space of stable peptides following peptide synthesis modification. To begin the procedure, attach a column filled with 50 milligrams of Rink Amide MBHA resin to both a benchtop vacuum manifold and a nitrogen or argon gas line via a three-way stopcock.

Add one to two milliliters of dichloromethane to the bed of resin, and swell the resin by gently agitating the mixture with a stream of inert gas bubbles for 10 minutes. Drain the resin with a rubber pipette bulb when finished. Then, add one to two milliliters of N-terminal Fmoc deprotection solution to the resin.