The oligopeptides (short chains of amino acids) were found to inhibit tyrosine, one of the key enzymes involved in melanin production, without the toxicity associated with some lightening ingredients.
In a recent study published in Nature’s Journal of Investigative Dermatology, the researchers described the inhibitory effects of oligopeptides P3 and P4 (amino acid sequences RADSRADC and YRSRKYSSWY respectively) on mushroom and human tyrosinase.
Strong inhibition at low concentrations
According to the study, P3 and P4 inhibit more tyrosinase at lower concentrations and are significantly less toxic than hydroquinone, one of the original skin lightening ingredients.
Like hydroquinone, P3 and 4 are competitive inhibitors to tyrosinase – they bind to the enzyme’s active site therefore blocking the binding of the substrate; but, unlike hydroquinone, they are not toxic to melanocytes (melanin producing cells).
P3 and P4 were 6- and 17-fold more potent inhibitors of mushroom tyrosinase than hydroquinone. Testing against human tyrosinase the oligopeptides were slightly less potent but still exhibited a stronger effect than hydroquinone.
At a concentration of 100 micro moles the peptides were able to inhibit human tyrosinase activity by 25-35 per cent. In addition, the scientists noticed a difference in the activity of the peptides depending on the substrate used in the reaction.
Tyrosinase catalyzes two reactions as part of its role in melanin synthesis: the first involves the conversion of dopa to dopaquinone and the second concerns the hydroxylation of tyrosine.
When L-dopa was used in the reaction, P3 showed the strongest inhibitory activity, according to the study. However, in the presence of L-tyrosine, it was P4 which had the strongest effect.
This suggests that the tyrosinase enzyme must have two catalytic sites, one for each substrate, according to the scientists.
They went on to investigate the toxicity of the peptides in comparison to hydroquinone. Using concentrations of 100 micromoles, hydroquinone was 100 per cent toxic after 24 hours, whereas P3 showed no toxic effects after 6 days and P4 only 7 per cent.
The combination of the high inhibitory activity and the low toxicity led the scientists to conclude that the peptides ‘may be ideal tyrosinase inhibitors’. The next step is to optimize the peptides’ ability to cross the skin barrier, in preparation for topical application, wrote the reseachers.
Source: Journal of Investigative Dermatology
2009, Volume 129, Pages 2242 – 2249
Short-sequence Oligopeptides with Inhibitory Activity against Mushroom and Human Tyrosinase
Anan Abu Ubeid, Longmei Zhao, Ying Wang, Basil M Hantash