Molecular diversity of peptidomimetics: approaches to the solid-phase synthesis of peptidosulfonamides.

In order to use the potential molecular diversity of the peptidosulfonamide peptidomimetics ultimately in libraries, approaches towards the solid-phase synthesis of peptidosulfonamides are a prerequisite. It is shown that peptidosulfonamides can be synthesized by solid-phase synthesis methods using either a Merrifield or a Tentagel resin. Better and more reproducible results are obtained using the latter resin. The possibility to prepare cyclic peptidosulfonamides was illustrated by the synthesis of cyclo-phenylalanyl psi[CH2S(O)2N]-glycine. However, translation of synthesis of peptidosulfonamides in solution to a solid-phase method was rather laborious and still requires careful optimization.