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

Abstract

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 1 H-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 timescale 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.

Diffusional Inhomogeneity of Probe Molecules in Chemically Cross-Linked Polymer Gels As Studied by Time-Dependent Diffusion NMR

“…Probe molecules used in this work have monodispersity and single component T 2 . In previous works, [21][22][23] we reported that probe molecules in solution have a single diffusion component. Therefore, we think that echo attenuation curvature is not attributed to diffusant polydispersity, trace solvents, T 2weighting, and artifacts, but host inhomogeneity.…”

Convenient and efficient synthesis of a lanthanide3+‐coordinated, diethylene triamine pentaacetic acid labeled biopolymer as an assay for the cholecystokinin B receptor

“…[1][2][3][4] Various polymer supports for the solid-phase synthesis of peptides have been studied. 5,6 The recent development of the incorporation of biopolymers with timeresolved fluorescence (TRF) for the imaging and therapy of tumors has become a stimulus for the design and synthesis of novel peptide polymers. [7][8][9] TRF assay systems are widely employed in highthroughput applications.…”

“…Two decades of peptide research have yielded a lot of information on the design, synthesis, and characterization of the structures of peptides 1–4. Various polymer supports for the solid‐phase synthesis of peptides have been studied 5, 6. The recent development of the incorporation of biopolymers with time‐resolved fluorescence (TRF) for the imaging and therapy of tumors has become a stimulus for the design and synthesis of novel peptide polymers 7–9.…”

Understanding Supported Reactions in Spherical Compartments: A General Algorithm To Model and Determine Rate Constants, Diffusion Coefficients, and Spatial Product Distributions

“…For small and medium-sized organic reagents, this leads to a reduction of the diffusion coefficient by a factor of typically 3-6 32 (e.g., the diffusion coefficient of BOC-Phe is reduced from D 0 ) 4.8 × 10 -6 cm 2 s -1 in DMF bulk solution to D e ) 0.9 × 10 -6 cm 2 s -1 in DMF-swollen polystyrene beads). 33 More dramatic decreases are observed for higher values of φ, high degrees of cross-linking, larger solute sizes, and strong solute-polymer interactions 32,34 (e.g., the diffusion coefficient of rhodamines is reduced from D 0 ) 2.8 × 10 -6 cm 2 s -1 in water 35 to D e ≈ 10 -7 cm 2 s -1 in solvent-swollen polymer beads 36 and to D e ≈ 5 × 10 -10 cm 2 s -1 in silica sol-gel materials). 23,37,38 For the bead size of d ) 100 µm considered here, the effective rate of the overall reaction shows a pronounced dependence on both k and D S .…”