Building blocks for the construction of bioorthogonally reactive peptides via solid-phase peptide synthesis Journal Article

Authors: Zeglis, B. M.; Emmetiere, F.; Pillarsetty, N.; Weissleder, R.; Lewis, J. S.; Reiner, T.
Article Title: Building blocks for the construction of bioorthogonally reactive peptides via solid-phase peptide synthesis
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. The earlier, the better! We report a novel synthesis of tetrazine-functionalized artificial amino acids, the creation of a model tetrazine-containing pentapeptide using solid-phase peptide synthesis, and the facile and rapid bioorthogonal radiolabeling of this peptide using a 89Zr- desferrioxamine-labeled trans-cyclooctene. © 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
Keywords: zirconium-89; positron emission tomography (pet); click chemistry; solid-phase peptide synthesis; bioorthogonal chemistry
Journal Title: ChemistryOpen
Volume: 3
Issue: 2
ISSN: 2191-1363
Publisher: Wiley V C H Verlag Gmbh  
Date Published: 2014-04-01
Start Page: 48
End Page: 53
Language: English
DOI: 10.1002/open.201402000
PROVIDER: scopus
PMCID: PMC4000166
PUBMED: 24808990
Notes: ChemistryOpen -- Export Date: 2 June 2014 -- CODEN: CHOPC -- Source: Scopus
Citation Impact
MSK Authors
  1. Brian Zeglis
    95 Zeglis
  2. Jason S Lewis
    384 Lewis
  3. Thomas Reiner
    128 Reiner