Journal article
The binding of vitamin B12 to transcobalamin(II); structural considerations for bioconjugate design—a molecular dynamics study
Molecular BioSystems, Vol.6(9), pp.1611-1618
2010
Abstract
As part of ongoing research into the use of vitamin B(12) (B(12); cobalamin; Cbl)-based bioconjugate approaches for the oral delivery of peptides/proteins, a molecular dynamics (MD) study of the binding of a cyanocobalamin-insulin (CN-Cbl-insulin) conjugate to human transcobalamin(II) (TCII) was recently reported that provides a qualitative picture of how the human insulin protein in its open "T-state" geometry affects CN-Cbl binding to TCII. This initial analysis revealed that the B22-B30 segment of the insulin B-chain acts as a long tether that connects the larger combined insulin A/B region to CN-Cbl when this conjugation is performed at the CN-Cbl ribose 5'-hydroxy position. The experimental support for this model of the binding interaction is provided by the consequences of the successful delivery of the CN-Cbl-insulin conjugate in the production of significantly decreased blood glucose levels in diabetic STZ-rat models. In efforts to provide a more detailed description of the (CN-Cbl)-TCII complex for modeling Cbl-based bioconjugate designs, the (CN-Cbl)-TCII system and a CN-Cbl conjugate incorporating a flexible tether composed of only the B22-B30 segment of human insulin have been examined by MD simulations. The implications of these simulations are discussed in terms of successful conjugate positioning on Cbl, especially when such sites are not apparent from the diffraction studies alone, and the possibilities, as yet not reported, for dual-tethered Cbl bioconjugates for multi-component drug delivery applications.
Details
- Title
- The binding of vitamin B12 to transcobalamin(II); structural considerations for bioconjugate design—a molecular dynamics study
- Authors/Creators
- D.G. Allis (Author/Creator) - Syracuse UniversityT.J. Fairchild (Author/Creator) - Murdoch UniversityR.P. Doyle (Author/Creator) - Syracuse University
- Publication Details
- Molecular BioSystems, Vol.6(9), pp.1611-1618
- Publisher
- Royal Society of Chemistry
- Identifiers
- 991005544567307891
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: InCites
Metrics
51 Record Views
InCites Highlights
These are selected metrics from InCites Benchmarking & Analytics tool, related to this output
- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 2 Chemistry
- 2.276 Metalloenzymes
- 2.276.1947 Radical Enzymes
- Web Of Science research areas
- Biochemistry & Molecular Biology
- ESI research areas
- Biology & Biochemistry