PSEUDO-PROLINES AS A SOLUBILIZING, STRUCTURE-DISRUPTING PROTECTION TECHNIQUE IN PEPTIDE-SYNTHESIS

Serine-, threonine-, and cysteine-derived cyclic building blocks (pseu do-prolines, Psi Pro) serve as reversible protecting groups for Ser, T hr, and Cys and prove to be versatile tools for overcoming some intrin sic problems in the field of peptide chemistry. The presence of Psi Pr o within a peptide sequence results in the disruption of beta-sheet st ructures considered as a source of intermolecular aggregation during c hain elongation, thus increasing solvation and coupling kinetics in pe ptide assembly. Due to their easy synthetic access and variability in the chemical stability by modifications introduced in the C-2 position of the oxazolidine/thiazolidine ring system, this protection techniqu e is adaptable to all common strategies in peptide synthesis. We descr ibe new types of Psi Pro building blocks suitable for standard Fmoc/tB u-based solid phase peptide synthesis, convergent strategies, and chem oselective ligation techniques as well as their use as a structure-dis rupting, solubilizing protection technique for the example of peptides generally considered as ''difficult sequences''.