Details are given of the preparation of two acid-labile peptide-resin linkage agents for use in solid phase custom peptide synthesis, viz. 4-hydroxymethylphenoxy-acetic acid and 3-methoxy-4-hydroxymethylphenoxyacetic acid. The latter is suitable for the preparation of peptide fragments bearing t-butyl-based side chain protecting groups.
Abstract Use of disulfide bonds for labile linkage in solid-phase custom peptide synthesis was investigated using polyacrylic polymers (Expansin). Three bifunctional disulfide handles were synthesized for the introduction of disulfide linkage to the synthesis support. This work showed that only N-Boc aminoethyl 2-propionic acid and N-Boc aminoethyl 2-isobutyric acid were fully compatible with Boc/Bzl peptide synthesis and trifluoromethane sulfonic acid side-chain protection. Qualitative and quantitative synthesis results were comparable to those obtained by conventional peptide synthesis using polyacrylic resins.
The resulting peptidyl-resins, which swelled in water or aqueous buffers, may be suitable for various biochemical applications, including use as peptide-resin conjugates for antibody production. Thiolysis by aqueous dithiothreitol released mercapto amide peptides suitable for various uses in solution (e.g., direct coupling with activated protein carrier, specific labeling in the mercapto amide group).