Change search
CiteExportLink to record
Permanent link

Direct link
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
SEAL by NMR: Glyco-Based Selenium-Labeled Affinity Ligands Detected by NMR Spectroscopy
Stockholm University, Faculty of Science, Department of Organic Chemistry.
Stockholm University, Faculty of Science, Department of Organic Chemistry.
Stockholm University, Faculty of Science, Department of Organic Chemistry.
2014 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 20, no 43, 13905-13908 p.Article in journal (Refereed) Published
Abstract [en]

We report a method for the screening of interactions between proteins and selenium-labeled carbohydrate ligands. SEAL by NMR is demonstrated with selenoglycosides binding to lectins where the selenium nucleus serves as an NMR-active handle and reports on binding through Se-77 NMR spectroscopy. In terms of overall sensitivity, this nucleus is comparable to C-13 NMR, while the NMR spectral width is ten times larger, yielding little overlap in Se-77 NMR spectroscopy, even for similar compounds. The studied ligands are singly selenated bioisosteres of methyl glycosides for which straightforward preparation methods are at hand and libraries can readily be generated. The strength of the approach lies in its simplicity, sensitivity to binding events, the tolerance to additives and the possibility of having several ligands in the assay. This study extends the increasing potential of selenium in structure biology and medicinal chemistry. We anticipate that SEAL by NMR will be a beneficial tool for the development of selenium-based bioactive compounds, such as glycomimetic drug candidates.

Place, publisher, year, edition, pages
2014. Vol. 20, no 43, 13905-13908 p.
Keyword [en]
Se-77 NMR spectroscopy, lectins, protein-ligand interactions, SEAL, selenoglycosides
National Category
Organic Chemistry
Research subject
Organic Chemistry
URN: urn:nbn:se:su:diva-109971DOI: 10.1002/chem.201404933ISI: 000343800700012OAI: diva2:768717
Swedish Research CouncilKnut and Alice Wallenberg Foundation


Available from: 2014-12-04 Created: 2014-12-02 Last updated: 2017-12-05Bibliographically approved
In thesis
1. The sweet side of molecular structure: NMR spectroscopic studies of glycans and their interactions with proteins
Open this publication in new window or tab >>The sweet side of molecular structure: NMR spectroscopic studies of glycans and their interactions with proteins
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In this thesis, within the topic of bioorganic chemistry, the molecular structure of carbohydrates has been studied. Carbohydrates, or glycans, are ubiquitous biomolecules exhibiting a wide range of biological roles. The specific functions of these molecules are largely determined by their interactions with proteins and molecular structure ultimately governs such specialized recognition events.

Glycan-binding proteins, such as lectins or enzymes, often interact with their sweet ligands in a transient fashion and nuclear magnetic resonance spectroscopy (NMR) is a viable technique to probe these complexes. In particular, ligand-based NMR techniques have been employed, typically in combination with other biophysical as well as biochemical and computational methods. The aim of this work has been to gain new insights about specific biological systems, to develop methods and to devise protocols for their studies.

The first two papers cover NMR-interaction studies of native ligands as well as inhibitor glycans with the enzyme hen egg-white lysozyme and the lectin botulinum neurotoxin type A. Screening experiments were performed to investigate ligand affinities and selectivities. Solution models in combination with X-ray crystal structures were compared in order to evaluate their agreement and the details of interactions.

A method for application in carbohydrate ligand NMR-screening was developed in paper three. The heteronucleus selenium was exploited as a reporter of selenoglycosides binding to lectins. 77Se NMR spectroscopy proved sensitive to binding events and the presented approach should be useful in large screenings of glycomimetic inhibitors.  In order to obtain sufficient amounts of glycans for bioorganic studies their production often relies on chemical synthesis. In the last paper, the structure of some conformationally highly activated glycosyl donors was thoroughly investigated and related to their reactivity in synthetic glycosylation reactions.  

Place, publisher, year, edition, pages
Stockholm: Department of Organic Chemistry, Stockholm University, 2015. 77 p.
bioorganic chemistry, glycans, ligand-based NMR, molecular simulations, protein-carbohydrate interactions, lectins, carbohydrate conformations, 77Se NMR, structure-reactivity relationships, super-armed donors
National Category
Organic Chemistry
Research subject
Organic Chemistry
urn:nbn:se:su:diva-112350 (URN)978-91-7649-083-9 (ISBN)
Public defence
2015-02-20, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 4: Manuscript.


Available from: 2015-01-29 Created: 2015-01-12 Last updated: 2017-10-11Bibliographically approved

Open Access in DiVA

fulltext(645 kB)34 downloads
File information
File name FULLTEXT01.pdfFile size 645 kBChecksum SHA-512
Type fulltextMimetype application/pdf

Other links

Publisher's full text

Search in DiVA

By author/editor
Hamark, ChristofferWidmalm, Göran
By organisation
Department of Organic Chemistry
In the same journal
Chemistry - A European Journal
Organic Chemistry

Search outside of DiVA

GoogleGoogle Scholar
Total: 34 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available


Altmetric score