The tandem chain extension aldol reaction used for synthesis of ketomethylene tripeptidomimetics targeting hPEPT1

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

  • Karina Thorn
  • Carsten Uhd Nielsen
  • Palle Jakobsen
  • Bente Steffansen
  • Charles K Zercher
  • Mikael Begtrup
The rationale for targeting the human di-/tripeptide transporter hPEPT1 for oral drug delivery has been well established by several drug and prodrug cases. The aim of this study was to synthesize novel ketomethylene modified tripeptidomimetics and to investigate their binding affinity for hPEPT1. Three related tripeptidomimetics of the structure H-Phe-¿[COCH(2)]-Ser(Bz)-X(aa)-OH were synthesized applying the tandem chain extension aldol reaction, where amino acid derived ß-keto imides were stereoselectively converted to a-substituted ¿-keto imides. In addition, three corresponding tripeptides, composed of amide bonds, were synthesized for comparison of binding affinities. The six investigated compounds were all defined as high affinity ligands (K(i)-values
OriginalsprogEngelsk
TidsskriftBioorganic & Medicinal Chemistry Letters
Vol/bind21
Udgave nummer15
Sider (fra-til)4597-4601
ISSN0960-894X
DOI
StatusUdgivet - aug. 2011

Bibliografisk note

Keywords: hPEPT1, ketomethylene, peptides, peptidomimetics, TCEA reaction

ID: 33687900