Liquid phase peptide synthesis by fragment condensation on a soluble polymer support, 6. The influence of peptide‐chain lengths of Boc‐oligopeptides on the coupling efficiencies of their C‐terminal amino acids in coupling reactions with polymer‐bound amino acids

The influence of both the peptide‐chain lengths of Boc‐oligopeptides and the degree of crosslinking of polymer supports on the coupling efficiencies of the C‐terminal amino acids of Bocoligopeptides in the coupling reactions with terminal free amino groups of amino acids linked to polymer supports was investigated. The coupling efficiencies of Boc‐oligopeptides (consisting of 3 to 10 amino acid residues) relative to those of Boc‐Val‐OH or Boc‐Met‐OH were determined by competitive coupling reactions with amino acids anchored to soluble and crosslinked polystyrene supports, using four systems of coupling reagents dicyclohexylcarbodiimide (DCC) + 1‐hydroxy‐1 H‐benzotriazole, DCC + N‐hydroxysuccinimide, DCC + N‐hydroxy‐5‐norbornene‐2,3‐dicarboximide, and N‐ethoxycarbonyl‐2‐ethoxy‐1,2‐dihydroquinoline. In the coupling reactions on soluble polystyrene supports, containing 1 mol‐% of an amino acid (per styrene monomeric unit), and on poly(styrene‐co‐divinylbenzene (1%)), containing 1 or 10 mol‐% of an amino acid, little influence of peptide‐chain lengths was observed. In reactions with amino acids anchored to poly(styrene‐co‐divinylbenzene (2%)) (containing 2 or 20 mol‐% of terminal amino groups), an increase in peptide‐chain length of Boc‐oligopeptides was found to reduce remarkably the coupling efficiencies of their C‐terminal amino acids. With poly(styrene‐co‐divinylbenzene (2%))s as supports, it was detected that amino groups are present which are sterically inaccessible for peptide fragments such as Boc‐Ala‐Ala‐Leu‐Leu‐Leu‐OH and Boc‐Ala‐Ala‐Leu‐Leu‐Leu‐Pro‐Pro‐Leu‐Leu‐Leu‐OH.