Method and apparatus for monitoring the automated synthesis of peptides

摘要

A method for monitoring a solid-phase peptide synthesis for free amino ends of unreacted peptide chains, the monitoring occurring at the end of each addition of a blocked amino acid to the peptide chains which are anchored to the solid phase. The method includes reacting the solid phase with a monitoring agent that forms a covalent bond with unblocked amino groups. The solid phase is then washed to remove the unreacted monitoring agent. A cleaving reagent is then used to selectively remove the covalently bound monitoring reagent from the ends of the unblocked peptide chains, while leaving the blocked chains intact. The amount of monitoring agent thus removed is then quantitatively measured to determine what proportion of the initial peptide chains failed to react with the blocked amino acid. Preferred monitoring agents for use in this process include trityl (triphenylmethyl) -based groups, and particularly preferred agents are trityl, monomethoxytrityl, dimethoxytrityl, and trimethoxytrityl chlorides.