Abstract:
:We recently reported a vitamin B(12) (B(12)) 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 B(12) 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 B(12)-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.
journal_name
ChemMedChemjournal_title
ChemMedChemauthors
Petrus AK,Allis DG,Smith RP,Fairchild TJ,Doyle RPdoi
10.1002/cmdc.200800346subject
Has Abstractpub_date
2009-03-01 00:00:00pages
421-6issue
3eissn
1860-7179issn
1860-7187journal_volume
4pub_type
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