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

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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
Original languageEnglish
JournalBioorganic & Medicinal Chemistry Letters
Volume21
Issue number15
Pages (from-to)4597-4601
ISSN0960-894X
DOIs
Publication statusPublished - Aug 2011

ID: 33687900