Synthesis and Evaluation of Cyclic Acetals of Serine Hydroxylamine for Amide-Forming KAHA Ligations


Date

2019-03-01

Publication Type

Journal Article

ETH Bibliography

yes

Citations

Altmetric

Data

Abstract

The α-ketoacid–hydroxylamine (KAHA) ligation allows the coupling of unprotected peptide segments. The most widely used variant employs a 5-membered cyclic hydroxylamine that forms a homoserine ester as the primary ligation product. While very effective, monomers that give canonical amino acid residues are in high demand. In order to preserve the stability and reactivity of cyclic hydroxylamines, but form a canonical amino acid residue upon ligation, we sought to prepare cyclic derivatives of serine hydroxylamine. An evaluation of several cyclization strategies led to cyclobutanone ketals as the leading structures. The preparation, stability, and amide-forming ligation of these serine-derived ketals are described.

Publication status

published

Editor

Book title

Journal / series

Volume

51 (5)

Pages / Article No.

1273 - 1283

Publisher

Thieme

Event

Edition / version

Methods

Software

Geographic location

Date collected

Date created

Subject

Ligation; Hydroxylamines; Acetals; Amides; Peptides

Organisational unit

03861 - Bode, Jeffrey W. / Bode, Jeffrey W. check_circle

Notes

Funding

169451 - Protein Synthesis with Chemoselective Ligations (SNF)

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