PEGYLATED PEPTIDES - SOLID-PHASE SYNTHESIS OF N(ALPHA)-PEGYLATED PEPTIDES USING FMOC STRATEGY

The feasibility of pegylating peptides by the solid-phase procedure wa s examined. Although polyethyleneglycol (PFG) was shown to be partiall y degraded by HF, the use of TFA was fully compatible with the PEG sys tem. Therefore, the Fmoc/tBu solid-phase strategy was utilized for the synthesis of a series of model tetra-, octa- and dodecapeptides, and the corresponding N(alpha)-pegylated peptides, which were prepared fro m common peptide-resin intermediates. PEG-OCH2-CO-Nle-OH, 3, proved to be an ideal reagent for N-terminal pegylation. This intermediate serv ed as a diagnostic for the determination of the number of PEG units/mo le of peptide. Solid-phase coupling reactions proceeded by standard pr ocedures using BOP-activation. The authentic pegylated peptides (readi ly purified by conventional of preparative HPLC) were fully characteri zed by amino acid analysis, H-1-NMR spectroscopy, analytical HPLC and laser desorption ionization mass spectrometry, leading to the values t hat are identical with the expected structures.