Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Aqueous synthesis of a small-molecule lanthanide chelator amenable to copper-free click chemistry

Stephanie Cara Bishop, Robert Winefield, Asokan Anbanandam, View ORCID ProfileJed Noah Lampe
doi: https://doi.org/10.1101/531087
Stephanie Cara Bishop
1 South University;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: scbishop@southuniversity.edu
Robert Winefield
2 Thermo-Fisher Scientific;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: robert.winefield@gmail.com
Asokan Anbanandam
3 University of South Florida;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: asokan1@usf.edu
Jed Noah Lampe
4 The University of Kansas Medical Center
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jed Noah Lampe
  • For correspondence: jlampe@kumc.edu
  • Abstract
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

The lanthanides (Ln3+), or rare earth elements, have proven to be useful tools for biomolecular NMR, X-ray crystallographic, and fluorescence analyses due to their unique 4f orbitals. However, their utility in biological applications has been limited because site-specific incorporation of a chelating element is required to ensure efficient binding of the free Ln3+ ion. Additionally, current Ln3+ chelator syntheses complicate efforts to directly incorporate Ln3+ chelators into proteins as the multi-step processes and a reliance on organic solvents promote protein denaturation and aggregation which are generally incompatible with direct incorporation into the protein of interest. To overcome these limitations, herein we describe a two-step aqueous synthesis of a small molecule lanthanide chelating agent amenable to site-specific incorporation into a protein using copper-free click chemistry with unnatural amino acids. The bioconjugate combines a diethylenetriaminepentaacetic acid (DTPA) chelating moiety with a clickable dibenzylcyclooctyne-amine (DBCO-amine) to facilitate the reaction with an azide containing unnatural amino acid. Incorporating the DBCO-amine avoids the use of the cytotoxic Cu2+ ion as a catalyst. The clickable lanthanide chelator (CLC) reagent reacted readily with p-azidophenylalanine (paF) without the need of a copper catalyst, thereby demonstrating proof-of-concept. Implementation of the orthogonal click chemistry reaction has the added advantage that the chelator can be used directly in a protein labeling reaction, without the need of extensive purification. Given the inherent advantages of Cu2+-free click chemistry, aqueous synthesis, and facile labeling, we believe that the CLC will find abundant use in both structural and biophysical studies of proteins and their complexes.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted January 26, 2019.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Aqueous synthesis of a small-molecule lanthanide chelator amenable to copper-free click chemistry
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Aqueous synthesis of a small-molecule lanthanide chelator amenable to copper-free click chemistry
Stephanie Cara Bishop, Robert Winefield, Asokan Anbanandam, Jed Noah Lampe
bioRxiv 531087; doi: https://doi.org/10.1101/531087
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Aqueous synthesis of a small-molecule lanthanide chelator amenable to copper-free click chemistry
Stephanie Cara Bishop, Robert Winefield, Asokan Anbanandam, Jed Noah Lampe
bioRxiv 531087; doi: https://doi.org/10.1101/531087

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One
Subject Areas
All Articles
  • Animal Behavior and Cognition (4117)
  • Biochemistry (8824)
  • Bioengineering (6528)
  • Bioinformatics (23481)
  • Biophysics (11800)
  • Cancer Biology (9218)
  • Cell Biology (13333)
  • Clinical Trials (138)
  • Developmental Biology (7440)
  • Ecology (11420)
  • Epidemiology (2066)
  • Evolutionary Biology (15166)
  • Genetics (10447)
  • Genomics (14054)
  • Immunology (9180)
  • Microbiology (22183)
  • Molecular Biology (8820)
  • Neuroscience (47610)
  • Paleontology (350)
  • Pathology (1430)
  • Pharmacology and Toxicology (2492)
  • Physiology (3735)
  • Plant Biology (8085)
  • Scientific Communication and Education (1438)
  • Synthetic Biology (2222)
  • Systems Biology (6042)
  • Zoology (1254)