PREPARATION AND APPLICATIONS OF POLYETHYLENE GLYCOL-POLYSTYRENE GRAFTRESIN SUPPORTS FOR SOLID-PHASE PEPTIDE-SYNTHESIS

Heterobifunctional polyethylene glycol (PEG) derivatives BocNH(CH2CH2O )nCONHCH2CO2H were attached cleanly onto aminomethyl copoly(styrene-1% divinylbenzene) (PS) resins by oxidation-reduction couplings mediated by tri-n-butylphosphine plus 2,2'-dipyridyl disulfide. The amount of PEG incorporated into the resultant PEG-PS graft resins can be control led through the degree of aminomethylation of the starting cross-linke d PS and/or by use of PEG derivatives of different molecular weight (i .e., approximately 2000 for nBAR = 45; approximately 4000 for nBAR = 9 0). The new PEG-PS supports, which have good swelling properties in an extended range of solvents, were evaluated as supports for stepwise s olid-phase peptide synthesis (SPPS) using tert.-butyloxycarbonyl (Boc) , 9-fluorenylmethyloxycarbonyl (Fmoc) or dithiasuccinoyl (Dts) for N(a lpha)-amino protection, along with compatible anchoring handles for th e C-terminal residue. Several peptide syntheses were carried out in pa rallel in order to compare PEG-PS supports with the corresponding pare nt PS resins; reproducible advantages were observed with PEG-PS. In ad dition, PEG-PS supports were shown to be uniquely suited for SPPS usin g acetonitrile as the solvent for all coupling steps and washes.