Biological tuning of synthetic tactics in solid-phase synthesis: application to A beta(1-42).
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.
Kim
Young Soo
YS
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Moss
Jason A
JA
Janda
Kim D
KD
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
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D013454:Sulfoxides; C075222:amyloid beta-protein (1-42); D008715:Methionine