Biological tuning of synthetic tactics in solid-phase synthesis: application to A beta(1-42)

Young Soo Kim, Jason A Moss, Kim D Janda

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)7776-8
Number of pages3
JournalJournal of Organic Chemistry
Volume69
Issue number22
DOIs
Publication statusPublished - 2004 Oct 29

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sulfoxide
Tuning
Peptides
Agglomeration
Resins

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Biological tuning of synthetic tactics in solid-phase synthesis : application to A beta(1-42). / Kim, Young Soo; Moss, Jason A; Janda, Kim D.

In: Journal of Organic Chemistry, Vol. 69, No. 22, 29.10.2004, p. 7776-8.

Research output: Contribution to journalArticle

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AU - Janda, Kim D

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AB - 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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