Anti-TYR monoclonal antibody, clone TQN471

The aim of this study was to identify novel antimelanogenic drugs from an epigenetic screening library containing various modulators targeting DNA methyltransferases, histone deacetylases, and other related enzymes/proteins. Of 141 drugs tested, K8 (4-((hydroxyamino)carbonyl)-N-(2-hydroxyethyl)-N-phenyl-benzeneacetamide; HPOB) was found to effectively inhibit the alpha-melanocyte-stimulating hormone (alpha-MSH)-induced melanin synthesis in B16-F10 murine melanoma cells without accompanying cytotoxicity. Additional experiments showed that K8 did not significantly reduce the mRNA and protein level of tyrosinase (TYR) or microphthalmia-associated transcription factor (MITF) in cells, but it potently inhibited the catalytic activity TYR in vitro (IC50, 1.1-1.5 mu M) as compared to beta-arbutin (IC50, 500-700 mu M) or kojic acid (IC50, 63 mu M). K8 showed copper chelating activity similar to kojic acid. Therefore, these data suggest that K8 inhibits cellular melanin synthesis not by downregulation of TYR protein expression through an epigenetic mechanism, but by direct inhibition of TYR catalytic activity through copper chelation. Metal chelating activity of K8 is not surprising because it is known to inhibit histone deacetylase (HDAC) 6 through zinc chelation. This study identified K8 as a potent inhibitor of cellular melanin synthesis, which may be useful for the treatment of hyperpigmentation disorders

Marine byproducts have become popular research themes due to their biological significance. The black sharkskin protein hydrolysate-based antioxidant peptides were firstly investigated in this study. The black sharkskin-derived novel antioxidant peptide demonstrating 81.05% free radical scavenging activity to ABTS at 500 mu g/mL, was identified to be Ala-Thr-Val-Tyr (ATVY). The crucially antioxidant interaction site of ATVY action on ABTS was determined to be Tyr in the N-terminal. ATVY reacted with ABTS to generate polyphenol-derived adducts which subsequently degraded into a purple compound. The MS/MS showed it was formed by covalently bonding through the phenol group of ATVY to the N group of ABTS. The free radical scavenging kinetics of ATVY on ABTS demonstrated a two-phase reaction process. These findings reveal the action mechanism of ATVY on ABTS, implying ATVY can be incorporated in the production of antioxidant food additives.