Synthesis of a tricyclic hexapeptide –via two consecutive ruthenium-catalyzed macrocyclization steps– with a constrained topology to mimic vancomycin's binding properties toward D-Ala-D-Ala dipeptide

Xin Yang; Johan Kemmink; Dirk T S Rijkers; Rob M J Liskamp

doi:10.1016/j.bmcl.2022.128887

Synthesis of a tricyclic hexapeptide –via two consecutive ruthenium-catalyzed macrocyclization steps– with a constrained topology to mimic vancomycin's binding properties toward D-Ala-D-Ala dipeptide

Xin Yang
, Johan Kemmink
, Dirk T S Rijkers
, Rob M J Liskamp

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

Abstract

A ring-closing metathesis (RCM) - peptide coupling - ruthenium-catalyzed azide alkyne cycloaddition (RuAAC) strategy was developed to synthesize a tricyclic hexapeptide in which the side chain to side chain connectivity pattern resulted in a mimic with a topology that effectively mimics the bioactivity of vancomycin as a potent binder of the bacterial cell wall D-Ala-D-Ala dipeptide sequence and more importantly being an effective inhibitor of bacterial growth.

Original language	English
Article number	128887
Number of pages	5
Journal	Bioorganic & Medicinal Chemistry Letters
Volume	73
Early online date	11 Jul 2022
DOIs	https://doi.org/10.1016/j.bmcl.2022.128887
Publication status	Published - 1 Oct 2022

Bibliographical note

Funding Information:
X.Y. acknowledges the China Scholarship Council (CRC) for financial support. We would like to thank, dr. Javier Sastre Toraño for performing the HRMS analyses, Linda Quarles van Ufford for measuring the MIC values, and Hao Zhang for his help with the modeling experiments.

Publisher Copyright:
© 2022 The Author(s)

Keywords

Macrocycles
Peptides
Peptidomimetics
Ring-closing metathesis
Ru-based azide alkyne cycloaddition

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10.1016/j.bmcl.2022.128887Licence: CC BY

1-s2.0-S0960894X22003638-mainFinal published version, 894 KBLicence: CC BY

Cite this

Yang, X., Kemmink, J., Rijkers, D. T. S., & Liskamp, R. M. J. (2022). Synthesis of a tricyclic hexapeptide –via two consecutive ruthenium-catalyzed macrocyclization steps– with a constrained topology to mimic vancomycin's binding properties toward D-Ala-D-Ala dipeptide. Bioorganic & Medicinal Chemistry Letters, 73, Article 128887. https://doi.org/10.1016/j.bmcl.2022.128887

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abstract = "A ring-closing metathesis (RCM) - peptide coupling - ruthenium-catalyzed azide alkyne cycloaddition (RuAAC) strategy was developed to synthesize a tricyclic hexapeptide in which the side chain to side chain connectivity pattern resulted in a mimic with a topology that effectively mimics the bioactivity of vancomycin as a potent binder of the bacterial cell wall D-Ala-D-Ala dipeptide sequence and more importantly being an effective inhibitor of bacterial growth.",

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author = "Xin Yang and Johan Kemmink and Rijkers, \{Dirk T S\} and Liskamp, \{Rob M J\}",

note = "Funding Information: X.Y. acknowledges the China Scholarship Council (CRC) for financial support. We would like to thank, dr. Javier Sastre Tora{\~n}o for performing the HRMS analyses, Linda Quarles van Ufford for measuring the MIC values, and Hao Zhang for his help with the modeling experiments. Publisher Copyright: {\textcopyright} 2022 The Author(s)",

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Synthesis of a tricyclic hexapeptide –via two consecutive ruthenium-catalyzed macrocyclization steps– with a constrained topology to mimic vancomycin's binding properties toward D-Ala-D-Ala dipeptide. / Yang, Xin; Kemmink, Johan; Rijkers, Dirk T S et al.
In: Bioorganic & Medicinal Chemistry Letters, Vol. 73, 128887, 01.10.2022.

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

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AB - A ring-closing metathesis (RCM) - peptide coupling - ruthenium-catalyzed azide alkyne cycloaddition (RuAAC) strategy was developed to synthesize a tricyclic hexapeptide in which the side chain to side chain connectivity pattern resulted in a mimic with a topology that effectively mimics the bioactivity of vancomycin as a potent binder of the bacterial cell wall D-Ala-D-Ala dipeptide sequence and more importantly being an effective inhibitor of bacterial growth.

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KW - Peptides

KW - Peptidomimetics

KW - Ring-closing metathesis

KW - Ru-based azide alkyne cycloaddition

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Synthesis of a tricyclic hexapeptide –via two consecutive ruthenium-catalyzed macrocyclization steps– with a constrained topology to mimic vancomycin's binding properties toward D-Ala-D-Ala dipeptide

Abstract

Bibliographical note

Keywords

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