Journal article
Exploring the implications of vitamin B12 conjugation to insulin on insulin receptor binding
ChemMedChem, Vol.4(3), pp.421-426
2009
Abstract
We recently reported a vitamin B12 (B12) based insulin conjugate that produced significantly decreased blood glucose levels in diabetic STZ-rat models. The results of this study posed a fundamental question, namely what implications does B12 conjugation have on insulin's interaction with the insulin receptor (IR)? To explore this question we used a combination of molecular dynamics simulations and immunoelectron microscopy, and the results are described herein. This investigation demonstrates that chemical modification of insulin by linking relatively large pendant groups does not inherently interfere with IR recognition. Furthermore, given that we have previously demonstrated a significant drop in blood glucose concentration following the oral administration of the B12-insulin bioconjugate used in this work, it is reasonable to conclude that the IR recognition described herein is associated with maintenance of biological activity for insulin. This outcome offers significant research scope for chemical modification of insulin with the purpose of improving oral-uptake efficiency.
Details
- Title
- Exploring the implications of vitamin B12 conjugation to insulin on insulin receptor binding
- Authors/Creators
- A.K. Petrus (Author/Creator)D.G. Allis (Author/Creator)R.P. Smith (Author/Creator)T.J. Fairchild (Author/Creator)R.P. Doyle (Author/Creator)
- Publication Details
- ChemMedChem, Vol.4(3), pp.421-426
- Publisher
- John Wiley and Sons Ltd
- Identifiers
- 991005544407607891
- Copyright
- © 2009 Wiley-VCH Verlag GmbH & Co. KGaA
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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Source: InCites
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- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.26 Diabetes
- 1.26.1099 Insulin Signaling
- Web Of Science research areas
- Chemistry, Medicinal
- Pharmacology & Pharmacy
- ESI research areas
- Pharmacology & Toxicology