Synthesis of Peptide‐PNA‐Peptide Conjugates by Semi‐Solid‐Phase Chemical Ligation Combined with Deactivation/Capture of Excess Reactants

Abstract

AbstractAn expeditious route to peptide‐PNA‐peptide conjugates following a two‐step native chemical ligation (NCL) strategy is described. A cys‐PNA‐thioester is immobilized on PEGA‐aldehyde resin by thiazolidine formation, followed by capping of excess resin aldehydes. The first NCL reaction is then performed with the immobilized PNA‐thioester, to give, after release from the solid support, the cys‐PNA‐peptide intermediate with relatively high purity. The latter is then converted into the target compound by the second NCL reaction with a thioester peptide, the excess of which is captured using a cysteine‐PEGA resin. The resulting peptide‐PNA‐peptide can then be readily isolated by a simple purification step. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)