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Fig. 2 Blood glucose levels for STZ-rats administered a single tail
vein injection (pH 7.0, 70 ml) of H2O (= control, Ctrl), 5.0 Â 10À7 mol
1 in H2O (B12), 5.0 Â 10À7 mol NaVO3 in H2O (V), or an equimolar
(5.0 Â 10À7 mol) solution of 1 + NaVO3 in H2O (V/B12) on day 7,
directly after measuring their blood glucose levels. The rats were
injected with STZ (55 mg kgÀ1) on day 0. The mean values represent
independent observations from 3 different animals in each group;
errors are Æ1 standard deviation.
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(V/B12) versus NaVO3 (V) were carried out using the streptozo-
tocin (STZ) rat model for Type 1 diabetes. Elevated blood glucose
levels were confirmed one week following intraperitoneal injection
of STZ (55 mg kgÀ1; levels rose from 94 Æ 7 (day 0) to 394 Æ 11
mg dlÀ1 (day 7), Fig. 2). Importantly, from day 8 onwards,
statistical analysis (student’s t-test) showed that the V/B12 con-
jugate mixture lowered glucose levels further than NaVO3 alone
(p o 0.05). Complex 1 did not significantly reduce blood glucose
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18 M. M. C. A. Castro, F. Avecilla, C. F. G. C. Geraldes, B. de Castro
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determined by potentiometry19b but are probably more reliable since
they are obtained directly from changes in 51V NMR chemical shifts
as a function of pH, whereas obtaining stability constants from
potentiometric titration results requires a good understanding of
solution speciation; (b) M. M. Castro, C. F. Geraldes, P. Gameiro, E.
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To summarize, we have synthesized novel vanadate con-
jugates of 3-(3-hydroxy-2-methyl-1H-pyridin-4-one)propylco-
balamin, the first vanadium–vitamin B12 bioconjugates with
potential as insulinomimetics. The conjugates were character-
ized by 1H and 51V NMR spectroscopy, mass spectrometry
and FTIR spectroscopy, and diffusion coefficients were deter-
mined using pulsed-field gradient-echo NMR spectroscopy
methods. Future studies include further testing of these com-
plexes and the preparation of other vanadium–vitamin B12
bioconjugates.
The authors thank Dr Anatoly Khitrin, Kent State Uni-
versity, for assistance with the pulsed-field gradient-echo
NMR spectroscopy measurements. NEB thanks the Juvenile
Diabetes Research Foundation (Grant 5-2005-943) for finan-
cial support of this research.
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27 Z. Schneider and A. Stroinski, Comprehensive B12, Walter de
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Notes and references
1 T. Scior, A. Guevara-Garcia, P. Bernard, Q.-T. Do, D. Domeyer
and S. Laufer, Mini-Rev. Med. Chem., 2005, 5, 995.
2 K. H. Thompson and C. Orvig, J. Inorg. Biochem., 2006, 100, 1925.
ꢀc
This journal is The Royal Society of Chemistry 2008
Chem. Commun., 2008, 3783–3785 | 3785