title: Native Serine Peptide Assembly: Scope and Utility.
abstract: This work develops serine peptide assembly (SPA), which complements and contrasts with classic native chemical ligation (NCL). Advances in reagent-less peptide bond formation have been applied to serine (and serine models) and a range ofC-terminal amino acids, including bulky residues that are not amenable to NCL. The particular appeal of SPA is preparative-scale segment condensations with zero racemization risk and favourable process mass intensity (PMI). Mechanistic studies support a previously proposed reaction pathway via an initial trans-esterification step. An understanding of the factors favouring this pathway relies on hard-soft acid-base theory, where mildly activated esters with the largest carbonyl positive charge are most reactive with hydroxy amines. NovelC-terminal activators have been discovered that enhance reactivity and give harmless by-products.
authors.affiliation: Department of Chemistry, University of California, Riverside, CA 92521 USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Pirrung
authors.affiliation: Department of Chemistry, University of California, Riverside, CA 92521 USA.
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Schreihans
keywords: acylation; amides; amino acids; nucleophilic substitution; transesterification