<abstract xmlns="http://www.w3.org/1999/xhtml"><p>A strategy for the design of new yttrium(III) tags consisting of sequences of naturally occurring amino acids is described. These tags are 4–6 amino acids in length and consist of aspartic and glutamic acids. The use of natural amino acids would allow these oligopeptides to be incorporated into recombinant proteins at the DNA level, enabling the protein to be Y(III)-labelled after protein isolation. This allows a radionuclide or heavy atom to be associated with the protein without the necessity of further synthetic modification. Suitable peptides able to chelate Y(III) in stable complexes were designed based on quantum-chemical calculations. The stability of complexes formed by these peptides was tested by isothermal titration calorimetry, giving dissociation constants in the micromolar range. The likely structure of the most tightly bound complex was inferred from a combination of NMR experiments and quantum-chemical calculations. This structure will serve as the basis for future optimizations.</p></abstract>

A strategy for the design of new yttrium(III) tags consisting of sequences of naturally occurring amino acids is described. These tags are 4–6 amino acids in length and consist of aspartic and glutamic acids. The use of natural amino acids would allow these oligopeptides to be incorporated into recombinant proteins at the DNA level, enabling the protein to be Y(III)-labelled after protein isolation. This allows a radionuclide or heavy atom to be associated with the protein without the necessity of further synthetic modification. Suitable peptides able to chelate Y(III) in stable complexes were designed based on quantum-chemical calculations. The stability of complexes formed by these peptides was tested by isothermal titration calorimetry, giving dissociation constants in the micromolar range. The likely structure of the most tightly bound complex was inferred from a combination of NMR experiments and quantum-chemical calculations. This structure will serve as the basis for future optimizations.

The design and NMR structure determination of yttrium-oligopeptide tags for recombinant proteins and antibodies

Department of Chemical Theory of Drugs, Faculty of Pharmacy

Institute of Chemistry, Faculty of Natural Sciences

Institute of Molecular Biology, Slovak Academy of Sciences

Acta Chimica Slovaca

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

A strategy for the design of new yttrium(III) tags consisting of sequences of naturally occurring amino acids is described. These tags are 4–6 amino acids in...

The design and NMR structure determination of yttrium-oligopeptide tags for recombinant proteins and antibodies

Publié en ligne: 19 déc. 2018

Pages: 120 - 133

DOI: https://doi.org/10.2478/acs-2018-0018

Mots clés
carboxylate ligands, density functional calculations, NMR spectroscopy, peptide design, yttrium tags

© 2018 Marcela Múdra et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

The design and NMR structure determination of yttrium-oligopeptide tags for recombinant proteins and antibodies

Publié en ligne: 19 déc. 2018

Pages: 120 - 133

DOI: https://doi.org/10.2478/acs-2018-0018

Mots cléscarboxylate ligands, density functional calculations, NMR spectroscopy, peptide design, yttrium tags

© 2018 Marcela Múdra et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Mots clés
carboxylate ligands, density functional calculations, NMR spectroscopy, peptide design, yttrium tags