Conformational properties of 1,4- and 1,5-substituted 1,2,3-triazole amino acids – building units for peptidic foldamers

Handle URI:
http://hdl.handle.net/10754/597834
Title:
Conformational properties of 1,4- and 1,5-substituted 1,2,3-triazole amino acids – building units for peptidic foldamers
Authors:
Kann, Nina; Johansson, Johan R.; Beke-Somfai, Tamás
Abstract:
© The Royal Society of Chemistry 2015. Peptidic foldamers have recently emerged as a novel class of artificial oligomers with properties and structural diversity similar to that of natural peptides, but possessing additional interesting features granting them great potential for applications in fields from nanotechnology to pharmaceuticals. Among these, foldamers containing 1,4- and 1,5-substitued triazole amino acids are easily prepared via the Cu- and Ru-catalyzed click reactions and may offer increased side chain variation, but their structural capabilities have not yet been widely explored. We here describe a systematic analysis of the conformational space of the two most important basic units, the 1,4-substitued (4Tzl) and the 1,5-substitued (5Tzl) 1,2,3-triazole amino acids, using quantum chemical calculations and NMR spectroscopy. Possible conformations of the two triazoles were scanned and their potential minima were located using several theoretical approaches (B3LYP/6-311++G(2d,2p), ωB97X-D/6-311++G(2d,2p), M06-2X/6-311++G(2d,2p) and MP2/6-311++G(2d,2p)) in different solvents. BOC-protected versions of 4Tzl and 5Tzl were also prepared via one step transformations and analyzed by 2D NOESY NMR. Theoretical results show 9 conformers for 5Tzl derivatives with relative energies lying close to each other, which may lead to a great structural diversity. NMR analysis also indicates that conformers preferring turn, helix and zig-zag secondary structures may coexist in solution. In contrast, 4Tzl has a much lower number of conformers, only 4, and these lack strong intraresidual interactions. This is again supported by NMR suggesting the presence of both extended and bent conformers. The structural information provided on these building units could be employed in future design of triazole foldamers. This journal is
Citation:
Kann N, Johansson JR, Beke-Somfai T (2015) Conformational properties of 1,4- and 1,5-substituted 1,2,3-triazole amino acids – building units for peptidic foldamers. Org Biomol Chem 13: 2776–2785. Available: http://dx.doi.org/10.1039/c4ob02359e.
Publisher:
Royal Society of Chemistry (RSC)
Journal:
Org. Biomol. Chem.
KAUST Grant Number:
Kuk No1
Issue Date:
2015
DOI:
10.1039/c4ob02359e
PubMed ID:
25605623
Type:
Article
ISSN:
1477-0520; 1477-0539
Sponsors:
We would like to thank Prof. Bengt Norden for inspiring discussions on this project. This work was funded by the King Abdullah University of Science and Technology (KAUST Kuk No1) and by the European Research Council (ERC).
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Publications Acknowledging KAUST Support

Full metadata record

DC FieldValue Language
dc.contributor.authorKann, Ninaen
dc.contributor.authorJohansson, Johan R.en
dc.contributor.authorBeke-Somfai, Tamásen
dc.date.accessioned2016-02-25T12:57:30Zen
dc.date.available2016-02-25T12:57:30Zen
dc.date.issued2015en
dc.identifier.citationKann N, Johansson JR, Beke-Somfai T (2015) Conformational properties of 1,4- and 1,5-substituted 1,2,3-triazole amino acids – building units for peptidic foldamers. Org Biomol Chem 13: 2776–2785. Available: http://dx.doi.org/10.1039/c4ob02359e.en
dc.identifier.issn1477-0520en
dc.identifier.issn1477-0539en
dc.identifier.pmid25605623en
dc.identifier.doi10.1039/c4ob02359een
dc.identifier.urihttp://hdl.handle.net/10754/597834en
dc.description.abstract© The Royal Society of Chemistry 2015. Peptidic foldamers have recently emerged as a novel class of artificial oligomers with properties and structural diversity similar to that of natural peptides, but possessing additional interesting features granting them great potential for applications in fields from nanotechnology to pharmaceuticals. Among these, foldamers containing 1,4- and 1,5-substitued triazole amino acids are easily prepared via the Cu- and Ru-catalyzed click reactions and may offer increased side chain variation, but their structural capabilities have not yet been widely explored. We here describe a systematic analysis of the conformational space of the two most important basic units, the 1,4-substitued (4Tzl) and the 1,5-substitued (5Tzl) 1,2,3-triazole amino acids, using quantum chemical calculations and NMR spectroscopy. Possible conformations of the two triazoles were scanned and their potential minima were located using several theoretical approaches (B3LYP/6-311++G(2d,2p), ωB97X-D/6-311++G(2d,2p), M06-2X/6-311++G(2d,2p) and MP2/6-311++G(2d,2p)) in different solvents. BOC-protected versions of 4Tzl and 5Tzl were also prepared via one step transformations and analyzed by 2D NOESY NMR. Theoretical results show 9 conformers for 5Tzl derivatives with relative energies lying close to each other, which may lead to a great structural diversity. NMR analysis also indicates that conformers preferring turn, helix and zig-zag secondary structures may coexist in solution. In contrast, 4Tzl has a much lower number of conformers, only 4, and these lack strong intraresidual interactions. This is again supported by NMR suggesting the presence of both extended and bent conformers. The structural information provided on these building units could be employed in future design of triazole foldamers. This journal isen
dc.description.sponsorshipWe would like to thank Prof. Bengt Norden for inspiring discussions on this project. This work was funded by the King Abdullah University of Science and Technology (KAUST Kuk No1) and by the European Research Council (ERC).en
dc.publisherRoyal Society of Chemistry (RSC)en
dc.titleConformational properties of 1,4- and 1,5-substituted 1,2,3-triazole amino acids – building units for peptidic foldamersen
dc.typeArticleen
dc.identifier.journalOrg. Biomol. Chem.en
dc.contributor.institutionChalmers University of Technology, Göteborg, Swedenen
dc.contributor.institutionAstraZeneca Sweden, Umea, Swedenen
dc.contributor.institutionMagyar Tudomanyos Akademia, Budapest, Hungaryen
kaust.grant.numberKuk No1en
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