Inhibition protein tyrosine phosphatases by an oxovanadium glutamate complex, Na₂[VO(Glu)₂(CH₃OH)](Glu = glutamate)

• Published in: Biometals 2010-12, Vol.23 (6), p.1139-1147
• Main Authors: Lu, Liping, Wang, Sulian, Zhu, Miaoli, Liu, Zhiwei, Guo, Maolin, Xing, Shu, Fu, Xueqi
• Format: Article
• Language: English
• Subjects: Amino acids; Biochemistry; Biomedical and Life Sciences; Cell Biology; Chemical synthesis; Coordination Complexes - chemical synthesis; Coordination Complexes - pharmacology; fluorescence; Glutamates - chemical synthesis; Glutamates - pharmacology; Humans; Inhibition; Inhibitor drugs; Insulin; Kinetics; Life Sciences; Medicine/Public Health; Metals; Microbiology; Oxovanadium-glutamate complex; Pharmacology/Toxicology; Plant Physiology; Protein Tyrosine Phosphatase, Non-Receptor Type 1 - antagonists & inhibitors; Protein tyrosine phosphatases; Protein Tyrosine Phosphatases - antagonists & inhibitors; Spectrometry, Fluorescence; Thermodynamics; Vanadates - pharmacology; Vanadium
• ISSN: 0966-0844; 1572-8773
• DOI: 10.1007/s10534-010-9363-8

The insulin-sensitizing effect of vanadium complexes has been linked to their ability to inhibit protein tyrosine phosphatases (PTPs). Considering that vanadium complexes may exchange in vivo with amino acids, forming in situ vanadium-amino acid complexes, we have synthesized and characterized an oxovanadium glutamate complex, Na₂[V(IV)O(Glu)₂(CH₃OH)]H₂O (1·H₂O). The complex showed potent inhibition against four human PTPs (PTP1B, TCPTP, HePTP, and SHP-1) with IC₅₀ in the 0.21-0.37 μM ranges. Fluorescence titration studies suggest that the complex binds to PTP1B with the formation of a 2:1 complex. Enzyme kinetics analysis using Lineweaver-Burk plots indicates a typical competitive inhibition mode.