glycylhistidyllysyne

Glycylhistidyllysyne is a synthetic tripeptide consisting of the amino acid residues glycine, histidine and lysine linked in that sequential order. The peptide is commonly synthesized by solid‐phase peptide synthesis using standard Fmoc chemistry, and its purity is verified by reversed‑phase HPLC and mass spectrometry. The presence of histidine provides a nitrogen‑rich side chain capable of coordinating metal ions, while the ε‑amino group of lysine offers a protonated amine under physiological conditions, imparting a net positive charge at neutral pH.

The tripeptide has been employed as a model system for studying metal chelation, nucleophilic catalysis and protein–peptide interactions. Its small size allows detailed NMR and X‑ray crystallographic investigations, revealing that the peptide backbone adopts a type II′ β‑turn conformation when bound to divalent metal ions such as Zn²⁺ or Cu²⁺. In enzymology, glycylhistidyllysyne is used to probe the catalytic mechanism of histidine‑dependent hydrolases and to screen for inhibitors that disrupt metal binding. Recent studies have also explored its potential as a carrier for drug delivery, exploiting the lysine residue to conjugate therapeutic molecules via amide linkages.

Because of its defined sequence and functional groups, glycylhistidyllysyne serves as a useful probe in biophysical assays, such as fluorescence resonance energy transfer and isothermal titration calorimetry, to quantify ligand affinity and kinetics. Although not found in natural proteins, the peptide’s modular design makes it a versatile tool in chemical biology and medicinal chemistry research.