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Biological tuning of synthetic tactics in solid-phase synthesis: application to A beta(1-42)
Young Soo Kim1, Jason A Moss, Kim D Janda
1Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Abstract:
The beta-amyloid(1-42) sequence has long been recognized as a challenging target for solid-phase peptide synthesis. We found that the known disaggregating role of Met-35 sulfoxide could be capitalized during stepwise solid-phase assembly of the A beta(1-42) peptide chain to mitigate on-resin peptide chain aggregation, a presumed major source of synthetic difficulties. Furthermore, we demonstrate a hitherto-unreported on-resin reduction of the sulfoxide "aggregation protecting group" to allow for standard cleavage protocols, obviating a separate solution-phase sulfoxide reduction step.
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