Building Blocks for the Construction of Bioorthogonally Reactive Peptides via Solid-Phase Peptide Synthesis
Version of Record online: 6 APR 2014
© 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Volume 3, Issue 2, pages 48–53, April 2014
How to Cite
Zeglis, B. M., Emmetiere, F., Pillarsetty, N., Weissleder, R., Lewis, J. S. and Reiner, T. (2014), Building Blocks for the Construction of Bioorthogonally Reactive Peptides via Solid-Phase Peptide Synthesis. ChemistryOpen, 3: 48–53. doi: 10.1002/open.201402000
- Issue online: 19 APR 2014
- Version of Record online: 6 APR 2014
- Manuscript Received: 17 FEB 2014
- US National Institute of Health (NIH). Grant Numbers: R01A138468, K25EB016673
- Brain Tumor Center of Memorial Sloan-Kettering Cancer Center
- bioorthogonal chemistry;
- click chemistry;
- positron emission tomography (PET);
- solid-phase peptide synthesis;
The need for post-synthetic modifications and reactive prosthetic groups has long been a limiting factor in the synthesis and study of peptidic and peptidomimetic imaging agents. In this regard, the application of biologically and chemically orthogonal reactions to the design and development of novel radiotracers has the potential to have far-reaching implications in both the laboratory and the clinic. Herein, we report the synthesis and development of a series of modular and versatile building blocks for inverse electron-demand Diels–Alder copper-free click chemistry: tetrazine-functionalized artificial amino acids. Following the development of a novel peptide coupling protocol for peptide synthesis in the presence of tetrazines, we successfully demonstrated its effectiveness and applicability. This versatile methodology has the potential to have a transformational impact, opening the door for the rapid, facile, and modular synthesis of bioorthogonally reactive peptide probes.