*3.2. Dipeptides Containing Tryptophan at the N-Terminus But Not at the C-Terminus Improved Memory Impairment*

Next, to evaluate the effect of the tryptophan position within the dipeptides, we assessed the effect of tryptophan, tyrosine, and the dipeptides WY and YW on spatial memory in the spontaneous alternation test. A single administration of 1 mg/kg WY dipeptide, but not tryptophan, tyrosine, or YW dipeptide, increased the spontaneous alternation (Figure 2A). We also tested the effect of tryptophan, methionine, and the dipeptides WM and MW on spatial memory. A single administration of 1 mg/kg WM peptide, but not tryptophan, methionine, or MW dipeptide, also increased the alternation (Figure 2B). These results suggested that the conformation of dipeptides with an N-terminal tryptophan is required to improve the spatial memory in amnestic mice.

**Figure 2.** The effects of the dipeptides and single amino acids of (A) WY and (B) WM on spatial memory in amnesic mice. Six-week-old Crl:CD1 male mice were orally administered 0 or 1 mg/kg of dipeptide or single amino acid (WY, YW, WM, MW, tryptophan (W), tyrosine (Y), and methionine (M)) and, 40 min later, injected intraperitoneally with 0.85 mg/kg of scopolamine. At 1 h after oral administration, each mouse was allowed to explore the Y-maze for 8 min. Spontaneous alternations were also measured. Data represent the mean ± SEM of 10 mice per group. The *p* values shown were calculated using the Dunnett's test. \* *p* < 0.05.
