Tyr-Phe

Aromatic amino acids in the brain function as precursors for the monoamine neurotransmitters serotonin (substrate tryptophan) and the catecholamines [dopamine, norepinephrine, epinephrine; substrate tyrosine (Tyr)]. Unlike almost all other neurotransmitter biosynthetic pathways, the rates of synthesis of serotonin and catecholamines in the brain are sensitive to local substrate concentrations, particularly in the ranges normally found in vivo. As a consequence, physiologic factors that influence brain pools of these amino acids, notably diet, influence their rates of conversion to neurotransmitter products, with functional consequences. This review focuses on Tyr and phenylalanine (Phe). Elevating brain Tyr concentrations stimulates catecholamine production, an effect exclusive to actively firing neurons. Increasing the amount of protein ingested, acutely (single meal) or chronically (intake over several days), raises brain Tyr concentrations and stimulates catecholamine synthesis. Phe, like Tyr, is a substrate for Tyr hydroxylase, the enzyme catalyzing the rate-limiting step in catecholamine synthesis. Tyr is the preferred substrate; consequently, unless Tyr concentrations are abnormally low, variations in Phe concentration do not affect catecholamine synthesis. Unlike Tyr, Phe does not demonstrate substrate inhibition. Hence, high concentrations of Phe do not inhibit catecholamine synthesis and probably are not responsible for the low production of catecholamines in subjects with phenylketonuria. Whereas neuronal catecholamine release varies directly with Tyr-induced changes in catecholamine synthesis, and brain functions linked pharmacologically to catecholamine neurons are predictably altered, the physiologic functions that utilize the link between Tyr supply and catecholamine synthesis/release are presently unknown. An attractive candidate is the passive monitoring of protein intake to influence protein-seeking behavior.

Phe-Tyr dipeptide which was investigated in Wakame food with greatest ACE-inhibitory activity is used as a pharmaceutical drug for the treatment of hypertension, cardiovascular diseases, and diabetic nephropathy. To improve the bioavailability of Phe-Tyr, a delivery system based on poly (lactic-co-glycolic acid) (PLGA) nanoparticles loaded with Phe-Tyr (Phe-Tyr-PLGA NPs) for treating hypertension and cardiovascular diseases was prepared in this study. In the experiments, poly(lactic-co-glycolic acid) (PLGA) and Phe-Tyr dipeptide-loaded PLGA nanoparticles were prepared using the double emulsion (w/o/w) method. The characterizations of the nanoparticles were performed with a UV-vis spectrometer, the Zeta-sizer system, and FTIR spectrometer. The optimum size of the Phe-Tyr dipeptide-loaded PLGA nanoparticle was obtained with a 213.8 nm average particle size, and a 0.061 polydispersity index, -19.5 mV zeta potential, 34% of loaded and 90.09% of encapsulation efficiency. From TEM analysis, it was clearly seen that the dipeptide loaded nanoparticles had the spherical and non-aggregated morphology and Phe-Tyr dipeptide loaded-PLGA nanoparticles were obtained successfully. Cell toxicity of nanoparticles at different concentrations was assayed with XTT methods on L929 fibroblast cells. This study determined that the nanoparticles have low toxicity at lower concentration and toxicity augmented with increasing concentration of dipeptide. To analyze the effect of solvents on structure of Phe-Tyr, Molecular dynamics simulation was performed with GROMACS program and molecular orbital calculations were carried out to obtain structural and electronic properties of dipeptide. Moreover, molecular docking calculations were also employed to model and predict protein-drug interactions.

The construction of potent peptide probes for selectively detecting denatured collagen is crucial for a variety of widespread diseases. However, all of the denatured collagen-targeting peptide probes found till date primarily utilized the repetitive (Gly-X-Y) n sequences with exclusively imino acids Pro and Hyp in the X and Y positions, which stabilized the triple helical conformation of the peptide probes, resulting in severe obstacles for their clinical applications. A novel series of peptide probes have been constructed by incorporating nonimino acids at the X position of the (GPO)3GXO(GPO)4 sequence, while the X-site residue is varied as Tyr, Phe, Asp, and Ala, respectively. Peptide probes FAM-GYO and FAM-GFO containing aromatic residues Tyr and Phe at the X position showed similarly high binding affinity and tissue-staining efficacy as the well-established peptide probe FAM-GPO, while peptide probes FAM-GDO and FAM-GAO with the corresponding charged residue Asp and the hydrophobic residue Ala indicated much weaker binding affinity and tissue-staining capability. Furthermore, FAM-GYO and FAM-GFO could specifically detect denatured collagen in different types of mouse connective tissues and efficiently stain various human pathological tissues. We have revealed for the first time that the incorporation of nonimino acids, particularly aromatic residues at the X and Y positions of the repetitive (Gly-X-Y) n sequences, may provide a convenient strategy to create novel robust collagen-targeting peptide probes, which have promising diagnostic applications in collagen-involved diseases.