Advancements in polymer resins for solid - phase peptide synthesis

The use of polymeric supports in solid-phase peptide synthesis has allowed for the facile, rapid synthesis of short peptides in a one bead/one sequence manner. This approach allows for screening peptide libraries for binding and catalytic activities. Once hits are found, the sequence of the active protein can be determined via mass spectrometry. However, problems arise when trying to create large libraries (on the order of 109) of peptides. The resins large enough to provide sufficient amounts of peptide sample for sequencing would occupy too great a volume in order to create large quantities. Conversely, attempting to fold a protein on resins with very high loading results in folding errors. In order to overcome these issues, we attempted to develop a novel coreshell polymer support, containing unprotected amine functional groups at low concentration on the resin surface and a large quantity of an amine, protected orthogonally to the conditions of solidstate peptide synthesis, in the core. In principle, this would allow for the synthesis of a sufficient quantity of fully folded proteins on the resin surface to screen for peptide activity while simultaneously synthesizing enough of the variable sequence in the interior of the resin to allow for a high yield of material for sequence determination. Thesis Supervisor: Jeremiah A. Johnson Title: Firmenich Career Development Assistant Professor