PSEUDO-PROLINES (PSI-PRO) FOR ACCESSING INACCESSIBLE PEPTIDES

Pseudo-prolines (Psi Pro) are introduced as a temporary protection tec hnique for serine, threonine and cysteine side chains in standard Fmoc /tBu solid-phase peptide synthesis (SPPS). The incorporation of these novel building blocks into a growing peptide chain proceeds by means o f the coupling of preformed, suitably protected Psi Pro dipeptides. Fo r the example of representative model peptides used in protein de novo design, the potential of Psi Pro, to solubilize otherwise sparingly o r completely insoluble peptides is demonstrated. Because of their intr insic propensity for preventing peptide aggregation and beta-sheet for mation, pseudo-prolines offer new possibilities for accessing large pe ptides by convergent strategies and chemoselective ligation techniques .