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Journal of Biomolecular NMR

, Volume 52, Issue 4, pp 365–370 | Cite as

Recombinant A22G–B31R-human insulin. A22 addition introduces conformational mobility in B chain C-terminus

  • Piotr Borowicz
  • Elżbieta Bednarek
  • Wojciech Bocian
  • Jerzy Sitkowski
  • Beata Jaworska
  • Jerzy Mikołajczyk
  • Tadeusz Głąbski
  • Dorota Stadnik
  • Weronika Surmacz
  • Monika Bogiel
  • Lech KozerskiEmail author
NMR structure note

Biological context

Wilde type insulin consists of two chains, having 21 and 30 aminoacids in chain A and B, respectively, held together by two disulfide bridges, namely A7C–B7C and A20C–B19C. There is also intra strand bridge in chain A; A6C–A11C. Insulin and its various derivatives are used in large amounts in the treatment of diabetes mellitus and are often manufactured on a large industrial scale. The modifications are aimed at altering the kinetics of drug release, often by favouring monomer over dimer (Hoeg-Jensen et al. 2005), the aim being to find a preparation that would maintain a constant level of glucose for an extended period of time. Commercial preparations can be long-acting [basal insulins such as glargine: A21N → G, B31R, B32R (Younis et al. 2002) or detemir: \({\text {B29}}^{{\text{K}}^{\epsilon}}\)

Keywords

Human Insulin Heteronuclear Single Quantum Coherence Native Insulin Modify Insulin Intracellular Inclusion Body 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This research was conducted within the frame of a Key Research Project under contract No. POIG.01.01.02-00-007/08-03. Part of these results was a research project supported from Ministry of Science and Higher Education funds reserved for science during a period of 2009–2012. Discussions with Prof. M.P. Williamson (University of Sheffield) concerning the text are gratefully acknowledged. Open image in new window Open image in new window

Supplementary material

10858_2012_9612_MOESM1_ESM.pdf (6 mb)
This includes experimental details, dilution experiments in water and water/acetonitrile solutions monitored by diffusion coefficient, Di [m2/s−1], CSI of Hα, Table 1S of 3 J (NH, Hα) vicinal coupling constants, constraints distribution and analysis (Figs 5S-10S), and Table 2S of 1H and 13C chemical shifts. Supplementary material 1 (PDF 6138 kb)

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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Piotr Borowicz
    • 1
  • Elżbieta Bednarek
    • 2
  • Wojciech Bocian
    • 2
    • 3
  • Jerzy Sitkowski
    • 2
    • 3
  • Beata Jaworska
    • 3
  • Jerzy Mikołajczyk
    • 1
  • Tadeusz Głąbski
    • 1
  • Dorota Stadnik
    • 1
  • Weronika Surmacz
    • 1
  • Monika Bogiel
    • 1
  • Lech Kozerski
    • 2
    • 3
    Email author
  1. 1.Institute of Biotechnology and AntibioticsWarsawPoland
  2. 2.National Medicines InstituteWarsawPoland
  3. 3.Institute of Organic Chemistry, Polish Academy of SciencesWarsawPoland

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