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Expanding on these data, additional modifications intended to increase hydrophobicity and decrease hydrogen bonding potential yielded N -hexanoic-Tyr-Ile-(6) aminohexanoic amide (dihexa), a potent cognitive-enhancing molecule that proved to be very stable, capable of inducing spinogenesis/synaptogenesis at picomolar concentrations, slowly cleared from the blood compartment, and sufficiently BBB-permeable