Protected aminooxyprolines for expedited library synthesis: application to Tsg101-directed proline-oxime containing peptides

Bioorg Med Chem Lett. 2008 Feb 1;18(3):1096-101. doi: 10.1016/j.bmcl.2007.12.003. Epub 2007 Dec 7.

Abstract

The stereoselective synthesis of aminooxy-containing proline analogues bearing Fmoc/Boc or Fmoc/Mtt protection that renders them suitable for incorporation into peptides using Fmoc protocols is reported. Acid-catalyzed unmasking at the completion of peptide synthesis yields free aminooxy-functionalities for oxime formation through reaction with libraries of aldehydes. This allows post solid-phase diversification strategies that may facilitate structure-activity relationship studies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Aldehydes / chemistry
  • Combinatorial Chemistry Techniques*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Endosomal Sorting Complexes Required for Transport
  • Humans
  • Molecular Structure
  • Oximes / chemical synthesis*
  • Oximes / chemistry
  • Peptides / chemical synthesis*
  • Peptides / chemistry
  • Proline / chemistry*
  • Protein Conformation
  • Stereoisomerism
  • Structure-Activity Relationship
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism*

Substances

  • Aldehydes
  • DNA-Binding Proteins
  • Endosomal Sorting Complexes Required for Transport
  • Oximes
  • Peptides
  • Transcription Factors
  • Tsg101 protein
  • Proline