Potentiating vanadium-evoked glucose metabolism by novel hydroxamate derivatives

Autor: Itzhak Goldwaser, Dov P. Grossman, Mati Fridkin, Sagit Hindi, Yoram Shechter
Rok vydání: 2002
Předmět:
Zdroj: Letters in Peptide Science. 9:235-254
ISSN: 1573-3904
0929-5666
DOI: 10.1007/bf02447549
Popis: L-glutamic acid (γ) monohydroxamate (L-Glu(γ)HXM) enhances the insulinomimetic activity of vanadium ions both in vitro and in vivo. Based on this ligand as a lead compound, and in order to delineate molecular features relevant to its anti-diabetic potential, 14 related derivatives, including short peptides, were synthesized by solution as well as by solid phase methodologies. In addition, hydroxamate derivatives of (+) pantothenic acid and D-biotin were prepared. The vanadium binding capacity of the hydroxamates synthesized was apparent, yet each had a different ligand-ions stoichiometry. The in vitro lipogenic potency of several compounds toward rat adipocytes was demonstrated. Thus, vanadium complexes of L-Gln(α)HXM, L-Glu(γ)HXM-Gly, L-Aad(δ)HXM, di-Glu-γ,γ-HXM and of (+) pantothenic acid hydroxamate exhibited 82, 79, 76, 39 and 39% of maximal insulin activity, respectively. L-Aad(δ)HXM, L-Glu(γ)HXM-Gly and (+) pantothenic acid hydroxamate – by themselves – were found to possess 24, 14 and 10% of maximal insulin activity, respectively. In vivo potency, however, of L-Gln(α)HXM vanadium complex in streptozocin-treated rat diabetic model was less apparent.
Databáze: OpenAIRE
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