Diffusion process of amino acids in polymer supports for solid-phase peptide synthesis as studied by pulsed-field-gradient spin-echo proton nuclear magnetic resonance

The diffusion coefficient (D) values of tert-butyloxycarbonyl-glycine, tert-butyloxycarbonyl-L-tryptophan, tert-butyloxycarbonyl-L-phenylalanine (Boc-Phe), and 9-fluorenylmethoxycarbonyl-L-phenylalanine in Merrifield polystyrene (MPS) gels, poly(ethylene glycol)-grafted polystyrene (PEG-PS) gels, and crosslinked ethoxylate acrylate (CLEAR) gels, as used in solid-phase peptide synthesis, were determined by the pulsed-field-gradient spin-echo H-1-NMR method. From these experimental results, it was found that the amino acids in MPS gels, PEG-PS gels, and CLEAR gels with N,N-dimethylformamide-d(7) (DMF-d(7)) as a solvent had multidiffusion components within a measurement time-scale of 10 ms. The D value of Boc-Phe in polystyrene gels (1% divinylbenzene crosslinked) with tetrahydrofuran-d(8) was much larger than that in the same gels with DMF-d(7). Furthermore, the required time in which an amino acid transferred from a reactive site to a reactive site was estimated, within which the solvents and amino acids in the polymer supports diffused in the swollen beads. (C) 2003 Wiley Periodicals, Inc.