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-phenylalanylΨ[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

Increased stability of peptidesulfonamide peptidomimetics towards protease catalyzed degradation

Replacement of amide bonds in peptides by sulfonamide moieties resulted in peptidosulfonamides with an increased stability towards protease catalyzed degradation. In addition to protection of the protease cleavage site, it was found that introduction of a sulfonamide also influenced the stability of adjacent amide bonds

Solid-phase synthesis of peptidosulfonamide containing peptides derived from Leu-enkephalin

Using Boc or Fmoc-protected β-substituted aminoethanesulfonyl chlorides (2-substituted taurylchlorides) the solid-phase synthesis of dipeptidosulfonamides as well as peptidosulfonamide containing peptides derived from Leu-enkephalin is described. The binding activity of the peptidosulfonamide YGGFL derivatives is reported