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

Karina Thorn; Carsten Uhd Nielsen; Palle Jakobsen; Bente Steffansen; Charles K Zercher; Mikael Begtrup

doi:10.1016/j.bmcl.2011.05.108

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

Karina Thorn, Carsten Uhd Nielsen, Palle Jakobsen, Bente Steffansen, Charles K Zercher, Mikael Begtrup

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

2 Citationer (Scopus)

Abstract

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

Originalsprog	Engelsk
Tidsskrift	Bioorganic & Medicinal Chemistry Letters
Vol/bind	21
Udgave nummer	15
Sider (fra-til)	4597-4601
ISSN	0960-894X
DOI	https://doi.org/10.1016/j.bmcl.2011.05.108
Status	Udgivet - aug. 2011

Bibliografisk note

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

Emneord

Det tidligere Farmaceutiske Fakultet

Adgang til dokumentet

10.1016/j.bmcl.2011.05.108

Citationsformater

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title = "The tandem chain extension aldol reaction used for synthesis of ketomethylene tripeptidomimetics targeting hPEPT1",

abstract = "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 ",

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author = "Karina Thorn and Nielsen, {Carsten Uhd} and Palle Jakobsen and Bente Steffansen and Zercher, {Charles K} and Mikael Begtrup",

note = "Keywords: hPEPT1, ketomethylene, peptides, peptidomimetics, TCEA reaction",

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AU - Thorn, Karina

AU - Nielsen, Carsten Uhd

AU - Jakobsen, Palle

AU - Steffansen, Bente

AU - Zercher, Charles K

AU - Begtrup, Mikael

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AB - 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

KW - Former Faculty of Pharmaceutical Sciences

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DO - 10.1016/j.bmcl.2011.05.108

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JO - Bioorganic & Medicinal Chemistry Letters

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