1,5-Disubstituted 1,2,3-Triazole-Containing Peptidotriazolamers: Design Principles for a Class of Versatile Peptidomimetics

Oliver Kracker; Jerzy Góra; Joanna Krzciuk-Gula; Antoine Marion; Beate Neumann; Hans-Georg Stammler; Anke Nieß; Iris Antes; Rafał Latajka; Norbert Sewald

doi:10.1002/chem.201704583

1,5-Disubstituted 1,2,3-Triazole-Containing Peptidotriazolamers: Design Principles for a Class of Versatile Peptidomimetics

Chemistry. 2018 Jan 19;24(4):953-961. doi: 10.1002/chem.201704583. Epub 2017 Dec 13.

Authors

Oliver Kracker¹, Jerzy Góra^{1

2}, Joanna Krzciuk-Gula^{1

2}, Antoine Marion³, Beate Neumann⁴, Hans-Georg Stammler⁴, Anke Nieß¹, Iris Antes³, Rafał Latajka², Norbert Sewald¹

Affiliations

¹ Organic and Bioorganic Chemistry, Department of Chemistry, Bielefeld University, PO Box 100131, 33501, Bielefeld, Germany.
² Department of Bioorganic Chemistry, Wrocław University of Science and Technology, Wybrzeze Wyspianskiego 27, 50-370, Wrocław, Poland.
³ Center for Integrated Protein Science, Department of Biosciences, TU Munich, Emil-Erlenmeyer-Forum 8, 85354, Freising, Germany.
⁴ Inorganic and Structural Chemistry, Department of Chemistry, Bielefeld University, PO Box 100131, 33501, Bielefeld, Germany.

PMID: 29160605
DOI: 10.1002/chem.201704583

Abstract

Peptidotriazolamers are hybrid foldamers combining features of peptides and triazolamers-repetitive peptidomimetic structures with triazoles replacing peptide bonds. We report on the synthesis of a new class of peptidomimetics, containing 1,5-disubstituted 1,2,3-triazoles in an alternating fashion with amide bonds and the analysis of their conformation in solid state and solution. Homo- or heterochiral peptidotriazolamers were obtained from enantiomerically pure propargylamines with stereogenic centers in the propargylic position and α-azido esters by ruthenium-catalyzed azide-alkyne cycloaddition (RuAAC) under microwave conditions in high yields. With such building blocks the peptidotriazolamers are readily available by solution phase synthesis. While the conformation of the homochiral peptidotriazolamer Boc-Ala[5Tz]Phe-Val[5Tz]Ala-Leu[5Tz]Val-OBzl resembles that of a β VIa1 turn, the heterochiral peptidotriazolamer Boc-d-Ala[5Tz]Phe-d-Val[5Tz]Ala-d-Leu[5Tz]Val-OBzl adopts a polyproline-like repetitive structure.

Keywords: conformational analysis; foldamers; peptidomimetics; ruthenium; triazoles.