δ-Peptides from RuAAC-Derived 1,5-Disubstituted Triazole Units

Handle URI:
http://hdl.handle.net/10754/600210
Title:
δ-Peptides from RuAAC-Derived 1,5-Disubstituted Triazole Units
Authors:
Johansson, Johan R.; Hermansson, Elin; Nordén, Bengt; Kann, Nina; Beke-Somfai, Tamás
Abstract:
Non-natural peptides with structures and functions similar to natural peptides have emerged lately in biomedical as well as nanotechnological contexts. They are interesting for pharmaceutical applications since they can adopt structures with new targeting potentials and because they are generally not prone to degradation by proteases. We report here a new set of peptidomimetics derived from δ-peptides, consisting of n units of a 1,5-disubstituted 1,2,3-triazole amino acid (5Tzl). The monomer was prepared using ruthenium-catalyzed azide-alkyne cycloaddition (RuAAC) chemistry using [RuCl2Cp]x as the catalyst, allowing for simpler purification and resulting in excellent yields. This achiral monomer was used to prepare peptide oligomers that are water soluble independent of peptide chain length. Conformational analysis and structural investigations of the oligomers were performed by 2D NOESY NMR experiments, and by quantum chemical calculations using the ωB97X-D functional. These data indicate that several conformations may co-exist with slight energetic differences. Together with their increased hydrophilicity, this feature of homo-5Tzl may prove essential for mimicking natural peptides composed of α-amino acids, where the various secondary structures are achieved by side chain effects and not by the rigidity of the peptide backbone. The improved synthetic method allows for facile variation of the 5Tzl amino acid side chains, further increasing the versatility of these compounds. A new set of non-natural peptides composed of 1,5-disubstituted 1,2,3-triazole amino acids is presented. These peptides benefit from: a) modular synthesis of the monomers, allowing variation of the side chains; b) increased solubility of the oligomers in water, irrespective of peptide length; c) flexibility of the backbone allowing these foldamers to adopt several conformations. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Citation:
Johansson JR, Hermansson E, Nordén B, Kann N, Beke-Somfai T (2014) δ-Peptides from RuAAC-Derived 1,5-Disubstituted Triazole Units. Eur J Org Chem 2014: 2703–2713. Available: http://dx.doi.org/10.1002/ejoc.201400018.
Publisher:
Wiley-Blackwell
Journal:
European Journal of Organic Chemistry
Issue Date:
14-Feb-2014
DOI:
10.1002/ejoc.201400018
Type:
Article
ISSN:
1434-193X
Sponsors:
This work was funded by the King Abdullah University of Science and Technology (KAUST Kuk No1) and by the European Research Council (ERC). The authors would like to thank Dr. Thomas Antonsson for useful discussions, Peter Bonn for assistance with HPLC purification of 8 and Annika Langborg Weinmann for running HRMS analyses.
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Full metadata record

DC FieldValue Language
dc.contributor.authorJohansson, Johan R.en
dc.contributor.authorHermansson, Elinen
dc.contributor.authorNordén, Bengten
dc.contributor.authorKann, Ninaen
dc.contributor.authorBeke-Somfai, Tamásen
dc.date.accessioned2016-02-28T06:45:20Zen
dc.date.available2016-02-28T06:45:20Zen
dc.date.issued2014-02-14en
dc.identifier.citationJohansson JR, Hermansson E, Nordén B, Kann N, Beke-Somfai T (2014) δ-Peptides from RuAAC-Derived 1,5-Disubstituted Triazole Units. Eur J Org Chem 2014: 2703–2713. Available: http://dx.doi.org/10.1002/ejoc.201400018.en
dc.identifier.issn1434-193Xen
dc.identifier.doi10.1002/ejoc.201400018en
dc.identifier.urihttp://hdl.handle.net/10754/600210en
dc.description.abstractNon-natural peptides with structures and functions similar to natural peptides have emerged lately in biomedical as well as nanotechnological contexts. They are interesting for pharmaceutical applications since they can adopt structures with new targeting potentials and because they are generally not prone to degradation by proteases. We report here a new set of peptidomimetics derived from δ-peptides, consisting of n units of a 1,5-disubstituted 1,2,3-triazole amino acid (5Tzl). The monomer was prepared using ruthenium-catalyzed azide-alkyne cycloaddition (RuAAC) chemistry using [RuCl2Cp]x as the catalyst, allowing for simpler purification and resulting in excellent yields. This achiral monomer was used to prepare peptide oligomers that are water soluble independent of peptide chain length. Conformational analysis and structural investigations of the oligomers were performed by 2D NOESY NMR experiments, and by quantum chemical calculations using the ωB97X-D functional. These data indicate that several conformations may co-exist with slight energetic differences. Together with their increased hydrophilicity, this feature of homo-5Tzl may prove essential for mimicking natural peptides composed of α-amino acids, where the various secondary structures are achieved by side chain effects and not by the rigidity of the peptide backbone. The improved synthetic method allows for facile variation of the 5Tzl amino acid side chains, further increasing the versatility of these compounds. A new set of non-natural peptides composed of 1,5-disubstituted 1,2,3-triazole amino acids is presented. These peptides benefit from: a) modular synthesis of the monomers, allowing variation of the side chains; b) increased solubility of the oligomers in water, irrespective of peptide length; c) flexibility of the backbone allowing these foldamers to adopt several conformations. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.en
dc.description.sponsorshipThis work was funded by the King Abdullah University of Science and Technology (KAUST Kuk No1) and by the European Research Council (ERC). The authors would like to thank Dr. Thomas Antonsson for useful discussions, Peter Bonn for assistance with HPLC purification of 8 and Annika Langborg Weinmann for running HRMS analyses.en
dc.publisherWiley-Blackwellen
dc.subjectClick chemistryen
dc.subjectConformation analysisen
dc.subjectCycloadditionen
dc.subjectFoldamersen
dc.subjectNitrogen heterocyclesen
dc.subjectPeptidomimeticsen
dc.titleδ-Peptides from RuAAC-Derived 1,5-Disubstituted Triazole Unitsen
dc.typeArticleen
dc.identifier.journalEuropean Journal of Organic Chemistryen
dc.contributor.institutionChalmers University of Technology, Göteborg, Swedenen
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