Purification and identification of xanthine oxidase inhibitory peptides from enzymatic hydrolysate of α-lactalbumin and bovine colostrum casein.

The development of food-derived Xanthine Oxidase (XO) inhibitors is critical to the treatment of hyperuricemia and oxidative stress-related disease. Few studies report on milk protein hydrolysates' XO inhibitory activity, with the mechanism of their interaction remaining elusive. Here, different commercial enzymes were used to hydrolyze α-lactalbumin and bovine colostrum casein. The two proteins hydrolyzed by alkaline protease exhibited the most potent XO inhibitory activity (bovine casein: IC50 = 0.13 mg mL-1; α-lactalbumin: IC50 = 0.28 mg mL-1). Eight potential XO inhibitory peptides including VYPFPGPI, GPVRGPFPIIV, VYPFPGPIPN, VYPFPGPIHN, QLKRFSFRSFIWR, LVYPFPGPIHN, AVFPSIVGR, and GFININSLR (IC50 of 4.67-8.02 mM) were purified and identified from alkaline protease hydrolysates by using gel filtration, LC-MS/MS and PeptideRanker. The most important role of inhibiting activity of peptides is linked to hydrophobic interactions and hydrogen bonding based on the results of molecular docking and molecular dynamics simulation. The enzymatic hydrolysate of α-lactalbumin and bovine colostrum casein could be a competitive candidates for hyperuricemia-resisting functional food.

Inhibiting Matrix Metalloproteinase-2 Activation by Perturbing Protein-Protein Interactions Using a Cyclic Peptide.

We report on a cyclic peptide that inhibits matrix metalloproteinase-2 (MMP2) activation with a low-nM-level potency. This inhibitor specifically binds to the D570-A583 epitope on proMMP2 and interferes with the protein-protein interaction (PPI) between proMMP2 and tissue inhibitor of metalloproteinases-2 (TIMP2), thereby preventing the TIMP2-assisted proMMP2 activation process. We developed this cyclic peptide inhibitor through an epitope-targeted library screening process and validated its binding to proMMP2. Using a human melanoma cell line, we demonstrated the cyclic peptide's ability to modulate cellular MMP2 activities and inhibit cell migration. These results provide the first successful example of targeting the PPI between proMMP2 and TIMP2, confirming the feasibility of an MMP2 inhibition strategy that has been sought after for 2 decades.

[Effect of specific immunoglobulin Y in the treatment of acute and chronic pharyngitis].

OBJECTIVE: To evaluate the effect and safety of the specific immunoglobulin Y (IgY) for treatment of acute and chronic pharyngitis. METHODS: Double-blind, randomized, placebo-controlled trial was conducted on 50 adults with acute pharyngitis. Experimental group received a 6 times-daily total 30 doses of IgY stomat-spray which contained specific immunoglobulin Y (titer = 512) prepared from the egg yolk of hens immunized with a variety of bacteria. Another open label trial included 50 patients, whose ages ranged from 21-69 years, including 25 cases of acute pharyngitis and 25 cases of chronic pharyngitis were also treated using IgY stomat-spray. The therapeutic effect were objectively evaluated 7 days later by the decreased scores based on both the symptoms and physical signs. If the symptom did not improve or became severe three days later, these patients with acute pharyngitis was inefficiency and antibiotic medicine would be added to them. RESULTS: In Double-blind trial, 8 cases (32%) received IgY had apparent effect with the decreased scores 5 or more than 5, 13 cases (52%) had effective with the decreased scores 3-4, and other 4 cases (16%) had inefficacy with the decreased scores only 2 or no more than 2. While in placebo-controlled group, only 2 (8%) cases had apparent effect, 5 (20%) cases showed effective and 18 (72%) cases had non-effect. The difference between the two groups was significant (chi 2 = 16.06, P < 0.01). In open label trial, 19 cases (38%) showed apparent effect, in which 14 cases were acute pharygitis. 23 cases (46%) had effective, in which 10 cases were acute pharyngitis. The left 8 cases (16%) had ineffective, in which one case was acute pharyngitis. There was significantly difference (chi 2 = 8.90, P < 0.05) between acute pharyngitis and chronic pharyngitis. An average of three months followup showed that there were no side effect or toxic effect and no allergic reaction. CONCLUSION: The IgY stomat-spray is a safe and effective agent in treating acute and chronic pharyngitis, especially for acute pharyngitis.