Solid-phase peptide synthesis in highly loaded conditions.

Abstract

The use of very highly substituted resins has been avoided for peptide synthesis due to the aggravation of chain-chain interactions within beads. To better evaluate this problem, a combined solvation-peptide synthesis approach was herein developed taking as models, several peptide-resins and with peptide contents values increasing up to near 85%. Influence of peptide sequence and loading to solvation characteristics of these compounds was observed. Moreover, chain-chain distance and chain concentration within the bead were also calculated in different loaded conditions. Of note, a severe shrinking of beads occurred during the α-amine deprotonation step only when in heavily loaded resins, thus suggesting the need for the modification of the solvent system at this step. Finally, the yields of different syntheses in low and heavily loaded conditions were comparable, thus indicating the feasibility of applying this latter "prohibitive" chemical synthesis protocol. We thought these results might be basically credited to the possibility, without the need of increasing molar excess of reactants, of carrying out the coupling reaction in higher concentration of reactants - near three to seven folds - favored by the use of smaller amount of resin. Additionally, the alteration in the solvent system at the α-amine deprotonation step might be also improving the peptide synthesis when in heavily loaded experimental protocol.

DOI: 10.1016/j.bioorg.2011.01.001

Cite this paper

@article{Nakaie2011SolidphasePS, title={Solid-phase peptide synthesis in highly loaded conditions.}, author={Cl{\'o}vis Ryuichi Nakaie and E. A. de Paiva Oliveira and Eduardo Festozo Vicente and Guita Nicolaewsky Jubilut and Sinval E. G. Souza and Reinaldo Marchetto and Eduardo Maffud Cilli}, journal={Bioorganic chemistry}, year={2011}, volume={39 2}, pages={101-9} }