Synthesis and Chemical and Biological Evaluation of a Glycine Tripeptide Chelate of Magnesium

Molecules. 2021 Apr 21;26(9):2419. doi: 10.3390/molecules26092419.

Abstract

Magnesium (Mg2+) plays a crucial role in over 80% of all metabolic functions. It is becoming increasingly apparent that magnesium deficiency (hypomagnesemia) may play an important role in chronic disease. To counteract magnesium deficiency, there is an unmet clinical need to develop new fully characterized, highly bioavailable, and substantially water-soluble magnesium supplements. To this end, triglycine (HG3), a tripeptide of the amino acid glycine, was chosen as a chelating ligand for magnesium, given its natural occurrence and water solubility, and entropically-driven metal binding. Herein, we discuss the synthesis, chemical and physical characterization, and cellular uptake of a magnesium triglycine chelate (MgG3), an octahedral complex with extraordinary water solubility and improved cellular uptake in CaCo-2 cells than select commonly used magnesium supplements.

Keywords: CaCo-2 cells; amino acid chelate; magnesium; solubility; triglycine.

MeSH terms

  • Cell Line, Tumor
  • Cells, Cultured
  • Chelating Agents / chemical synthesis
  • Chelating Agents / chemistry*
  • Chelating Agents / pharmacology*
  • Chemistry Techniques, Synthetic
  • Glycine / chemistry*
  • Humans
  • Magnesium / chemistry*
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Oligopeptides / chemical synthesis
  • Oligopeptides / chemistry*
  • Oligopeptides / pharmacology*
  • Solubility
  • Structure-Activity Relationship

Substances

  • Chelating Agents
  • Oligopeptides
  • Magnesium
  • Glycine