Pegylated peptides I: Solid-phase synthesis of N alpha-pegylated peptides using Fmoc strategy.
The feasibility of pegylating peptides by the solid-phase procedure was examined. Although polyethyleneglycol (PEG) was shown to be partially degraded by HF, the use of TFA was fully compatible with the PEG system. 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 from common peptide-resin intermediates. PEG-OCH2-CO-Nle-OH, 3, proved to be an ideal reagent for N-terminal pegylation. This intermediate served as a diagnostic for the determination of the number of PEG units/mole of peptide. Solid-phase coupling reactions proceeded by standard procedures using BOP-activation. The authentic pegylated peptides (readily purified by conventional methods of preparative HPLC) were fully characterized by amino acid analysis, 1H-NMR spectroscopy, analytical HPLC and laser desorption ionization mass spectrometry, leading to the values that are identical with the expected structures.
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Peptide Research Department, Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ 07110.
Felix
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D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D001426:Bacterial Proteins / Q000138:chemical synthesis; D005449:Fluorenes / Q000737:chemistry*; D016056:Immunodominant Epitopes / Q000737:chemistry; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis*; D010963:Plasmodium falciparum; D011092:Polyethylene Glycols / Q000737:chemistry*
D000596:Amino Acids; D001426:Bacterial Proteins; D005449:Fluorenes; D016056:Immunodominant Epitopes; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D010455:Peptides; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol