Synthesis of Conformationally Constrained Peptidomimetics using Multicomponent Reactions

R. Scheffelaar, R.A.K. Nijenhuis, M. Paravidino, M. Lutz, A.L Spek, A.W. Ehlers, F.J.J. de Kanter, M.B. Groen, R.V.A. Orru, E. Ruijter

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

A novel modular synthetic approach toward constrained peptidomimetics is reported. The approach involves a highly efficient three-step sequence including two multicomponent reactions, thus allowing unprecedented diversification of both the peptide moieties and the turn-inducing scaffold. The turn-inducing properties of the dihydropyridone scaffold were evaluated by molecular modeling, X-ray crystallography, and NMR studies of a resulting peptidomimetic. Although modeling studies point toward a type IV β-turn-like structure, the X-ray crystal structure and NMR studies indicate an open turn structure. © 2009 American Chemical Society.
Original languageEnglish
Pages (from-to)660-668
JournalJournal of Organic Chemistry
Volume74
Issue number2
DOIs
Publication statusPublished - 2009

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Peptidomimetics
Scaffolds
Nuclear magnetic resonance
Molecular modeling
X ray crystallography
Crystal structure
X rays
Peptides

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Scheffelaar, R., Nijenhuis, R. A. K., Paravidino, M., Lutz, M., Spek, A. L., Ehlers, A. W., ... Ruijter, E. (2009). Synthesis of Conformationally Constrained Peptidomimetics using Multicomponent Reactions. Journal of Organic Chemistry, 74(2), 660-668. https://doi.org/10.1021/jo802052j
Scheffelaar, R. ; Nijenhuis, R.A.K. ; Paravidino, M. ; Lutz, M. ; Spek, A.L ; Ehlers, A.W. ; de Kanter, F.J.J. ; Groen, M.B. ; Orru, R.V.A. ; Ruijter, E. / Synthesis of Conformationally Constrained Peptidomimetics using Multicomponent Reactions. In: Journal of Organic Chemistry. 2009 ; Vol. 74, No. 2. pp. 660-668.
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abstract = "A novel modular synthetic approach toward constrained peptidomimetics is reported. The approach involves a highly efficient three-step sequence including two multicomponent reactions, thus allowing unprecedented diversification of both the peptide moieties and the turn-inducing scaffold. The turn-inducing properties of the dihydropyridone scaffold were evaluated by molecular modeling, X-ray crystallography, and NMR studies of a resulting peptidomimetic. Although modeling studies point toward a type IV β-turn-like structure, the X-ray crystal structure and NMR studies indicate an open turn structure. {\circledC} 2009 American Chemical Society.",
author = "R. Scheffelaar and R.A.K. Nijenhuis and M. Paravidino and M. Lutz and A.L Spek and A.W. Ehlers and {de Kanter}, F.J.J. and M.B. Groen and R.V.A. Orru and E. Ruijter",
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Scheffelaar, R, Nijenhuis, RAK, Paravidino, M, Lutz, M, Spek, AL, Ehlers, AW, de Kanter, FJJ, Groen, MB, Orru, RVA & Ruijter, E 2009, 'Synthesis of Conformationally Constrained Peptidomimetics using Multicomponent Reactions' Journal of Organic Chemistry, vol. 74, no. 2, pp. 660-668. https://doi.org/10.1021/jo802052j

Synthesis of Conformationally Constrained Peptidomimetics using Multicomponent Reactions. / Scheffelaar, R.; Nijenhuis, R.A.K.; Paravidino, M.; Lutz, M.; Spek, A.L; Ehlers, A.W.; de Kanter, F.J.J.; Groen, M.B.; Orru, R.V.A.; Ruijter, E.

In: Journal of Organic Chemistry, Vol. 74, No. 2, 2009, p. 660-668.

Research output: Contribution to Journal › Article › Academic › peer-review

TY - JOUR

T1 - Synthesis of Conformationally Constrained Peptidomimetics using Multicomponent Reactions

AU - Scheffelaar, R.

AU - Nijenhuis, R.A.K.

AU - Paravidino, M.

AU - Lutz, M.

AU - Spek, A.L

AU - Ehlers, A.W.

AU - de Kanter, F.J.J.

AU - Groen, M.B.

AU - Orru, R.V.A.

AU - Ruijter, E.

PY - 2009

Y1 - 2009

N2 - A novel modular synthetic approach toward constrained peptidomimetics is reported. The approach involves a highly efficient three-step sequence including two multicomponent reactions, thus allowing unprecedented diversification of both the peptide moieties and the turn-inducing scaffold. The turn-inducing properties of the dihydropyridone scaffold were evaluated by molecular modeling, X-ray crystallography, and NMR studies of a resulting peptidomimetic. Although modeling studies point toward a type IV β-turn-like structure, the X-ray crystal structure and NMR studies indicate an open turn structure. © 2009 American Chemical Society.

AB - A novel modular synthetic approach toward constrained peptidomimetics is reported. The approach involves a highly efficient three-step sequence including two multicomponent reactions, thus allowing unprecedented diversification of both the peptide moieties and the turn-inducing scaffold. The turn-inducing properties of the dihydropyridone scaffold were evaluated by molecular modeling, X-ray crystallography, and NMR studies of a resulting peptidomimetic. Although modeling studies point toward a type IV β-turn-like structure, the X-ray crystal structure and NMR studies indicate an open turn structure. © 2009 American Chemical Society.

U2 - 10.1021/jo802052j

DO - 10.1021/jo802052j

M3 - Article

VL - 74

SP - 660

EP - 668

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

SN - 0022-3263

IS - 2

ER -

Scheffelaar R, Nijenhuis RAK, Paravidino M, Lutz M, Spek AL, Ehlers AW et al. Synthesis of Conformationally Constrained Peptidomimetics using Multicomponent Reactions. Journal of Organic Chemistry. 2009;74(2):660-668. https://doi.org/10.1021/jo802052j

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