title: Fmoc solid-phase synthesis of C-terminal modified peptides by formation of a backbone cyclic urethane moiety.
abstract: C-terminally modified peptides are of high significance due to the therapeutic properties that accompany various C-terminal functional groups and the ability to manipulate them for further applications. Thus, there is a great necessity for an effective solid phase technique for the synthesis of C-terminally modified peptides. Here, we report a universal solid phase strategy for the synthesis of various C-terminal modified peptides which is independent of the type of resins, linkers, and unnatural moieties typically needed for C-terminal modifications. The technique proceeds by the modification of C-terminal serine to a cyclic urethane moiety which results in the activation of the backbone amide chain for nucleophilic displacement by various nucleophiles to generate C-terminally modified acids, esters, N-aryl amides, and alcohols. This cyclic urethane technique (CUT) also provides a general strategy for synthesis of C-terminal protected peptides that can be used for convergent synthesis of large peptides. The C-terminal protecting groups are cleaved by facile hydrolysis to release the free peptide.
authors.affiliation: Department of Chemistry, Seton Hall University, 400 South Orange Ave, South Orange, NJ 07079, USA. monika.raj@shu.edu.
authors.forename: Hader E
authors.initials: HE
authors.lastname: Elashal
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Cohen
authors.forename: Monika
authors.initials: M
authors.lastname: Raj