Peptide Segment Separation by Tertiary Peptide Bonds. Synthesis and Conformational Analysis of Cross-Linked Polystyrene Resin-Bound Human Proinsulin C-Peptide Fragments

Abstract

Abstract In order to clarify the role of tertiary peptide bonds in the conformational development of protected peptides in organic solvents, cross-linked polystyrene resin-bound human proinsulin C-peptide fragments were prepared by a fragment condensation method. For the purpose of clarifying the role of tertiary peptide bonds, it is indispensable to force coupling reactions to completion; the addition of HFIP in coupling reactions in CH2Cl2 was significantly effective for their completion when they did not proceed smoothly. The conformational behavior of resin-bound human proinsulin C-peptide fragments in CH2Cl2 was successively investigated using IR absorption spectroscopy. Two Pro residues forming tertiary peptide bonds played the role of stopping the development of helix and β-sheet structures in peptides, and the structure of N- and C-terminiand side-chain-protected human proinsulin C-peptide could be regarded as being assembled with peptide segment structures separated by the two Pro residues. When a peptide segment had a high helix-forming potential, a Pro residue in an N-terminal part of the peptide segment promoted its helix formation. β-Sheet structures formed by peptide segments in CH2Cl2 were easily disrupted by a strong electron-acceptor solvent of HFIP, suggesting that the β-sheet structure disruption of resin-bound peptides is important in achieving efficient coupling reactions.