Methods for the synthesis of arginine-containing peptides

A method for deprotecting a peptide comprising a Mtr-, Pmc- or Pbf-side chain protected arginine and at least an amino acid carrying an electron rich aromatic side chain, said method comprising the steps of:

• a.) solubilizing the peptide in a solvent mixture of at least one aprotic organic solvent, a thiol scavenger, and either a protic solvent or a carboxylic acid selected from the group of formic acid, acetic acid and/or trifluoroacetic acid or a mixture thereof, wherein the amount of the carboxylic acid is selected in the range of 5 to 30%, based on the total volume of the solvent mixture, followed by
• b.) mixing the solution obtained in step a.) with a mixture of (i) a carboxylic acid selected from the group of formic acid, acetic acid and/or trifluoroacetic acid and (ii) a sulfonic acid selected from the group of methanesulfonic acid, trifluoromethane sulfonic acid, benzene sulfonic acid and/or p-toluene sulfonic acid, with the proviso that the total amount (by moles) of the carboxylic acid used in step a.) and b.) is higher than the total amount of the sulfonic acid.