Building Blocks for the Construction of Bioorthogonally Reactive Peptides via Solid‐Phase Peptide Synthesis

ChemistryOpen

Dr. Brian M. Zeglis²  Fabien Emmetiere²  Dr. Nagavarakishore Pillarsetty²  Prof. Ralph Weissleder³  Prof. Jason S. Lewis¹ 

[1] E-mail address: 关键词: bioorthogonal chemistry;    click chemistry;    positron emission tomography (PET);    solid-phase peptide synthesis;    zirconium-89;   

DOI  :  10.1002/open.201402000

来源: Wiley

【 摘 要 】

Abstract

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.

【 授权许可】

CC BY-NC-ND   
© 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

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.