title: Biological tuning of synthetic tactics in solid-phase synthesis: application to A beta(1-42).
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.
authors.affiliation: Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Young Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: Jason A
authors.initials: JA
authors.lastname: Moss
authors.forename: Kim D
authors.initials: KD
authors.lastname: Janda
mesh_terms: D016229:Amyloid beta-Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D002625:Chemistry, Organic / Q000379:methods*; D008715:Methionine / Q000031:analogs & derivatives / Q000737:chemistry; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry; D013454:Sulfoxides / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D013454:Sulfoxides; C075222:amyloid beta-protein (1-42); D008715:Methionine