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Dihexa (N-hexanoic-Tyr-Ile-Ahx-NH₂) is a metabolically stabilized, blood-brain-barrier-permeable peptidomimetic analog of angiotensin IV. The molecule binds hepatocyte growth factor (HGF) with high affinity and potentiates HGF-dependent dimerization and autophosphorylation of the c-Met receptor tyrosine kinase. In dissociated primary neuronal cultures and organotypic hippocampal slice preparations this interaction produces a measurable increase in dendritic spine density, particularly of mature mushroom-type spines, together with elevated expression of postsynaptic density proteins and facilitation of long-term potentiation. Parallel in-vivo experiments in rodent models document corresponding elevations in hippocampal synaptic markers, enhanced process outgrowth, and altered performance on hippocampus-dependent behavioral assays.
Product Name: Dihexa
CAS Number: 1401708-83-5
Molecular Formula: C₂₇H₄₄N₄O₅
Molecular Weight: 504.66 g/mol
PubMed ID: 129010512
Dihexa (N-hexanoic-Tyr-Ile-Ahx-NH₂) is a metabolically stabilized, blood-brain-barrier-permeable peptidomimetic derived from the hexapeptide angiotensin IV. N-terminal hexanoylation together with C-terminal aminohexanoic amidation increases overall lipophilicity and confers resistance to aminopeptidases and other circulating peptidases, allowing the intact molecule to reach measurable concentrations in brain tissue after peripheral administration. The compound binds hepatocyte growth factor (HGF) with nanomolar affinity and functions as a potent potentiator of HGF-dependent c-Met receptor dimerization and autophosphorylation. In dissociated primary hippocampal and cortical neuronal cultures and in organotypic hippocampal slice preparations this interaction produces a time- and concentration-dependent increase in dendritic spine density, preferential formation and stabilization of mature mushroom-type spines, upregulation of postsynaptic-density proteins including PSD-95, and facilitation of activity-dependent long-term potentiation at Schaffer collateral–CA1 synapses. Parallel in-vivo studies in rodent models document corresponding elevations in hippocampal synaptic-marker immunoreactivity, enhanced neurite and process outgrowth, and statistically significant changes in performance metrics on hippocampus-dependent spatial and recognition-memory tasks.
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