Current Topics in Medicinal Chemistry

Allen B. Reitz
Fox Chase Chemical Diversity Center, Inc.
Doylestown, PA
USA

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Novel Pentapeptide Activators of Mammalian and Mushroom Tyrosinase

Author(s): Anan Abu Ubeid and Basil M. Hantash

Affiliation: Escape Therapeutics, Inc., 5941 Optical Court, San Jose, CA 95138, USA.

Keywords: Allosteric activation, melanin content, melanoma, pentapeptide, tanning beds, tyrosinase.

Graphical Abstract:


Abstract:

Melanoma incidence continues to rise due to intentional exposure to ultraviolet radiation (UVR) from sunlight and indoor tanning beds. Eumelanin exhibits photoprotective effects; thus, agents that induce its synthesis offer a means for sunless tanning without UVR damage. Herein, we report the development of two pentapeptides, P9 and P10, capable of enhancing melanin synthesis in B16 melanoma cells by activating mushroom and mouse tyrosinases without any effect on cell viability or proliferation. P9 and P10 significantly increased melanin content in a dose-dependent manner comparable to the positive controls, IBMX, scoparone, and α-MSH. However, unlike IBMX and scoparone, but similar to α-MSH, P9 and P10 were able to reverse 6BH4-dependent tyrosinase inhibition. We hypothesize that P9 and P10 allosterically activate tyrosinase and consequently enhance epidermal melanin synthesis. P9 and P10 may offer an alternative to tanning bed use and non-photoprotective tanning products. Moreover, sustained increase of melanin content in skin has the potential to reduce symptoms of photosensitivity disorders such as erythropoietic protoporphyria (EPP), solar urticaria (SU) and polymorphic light eruption (PLE), which lack fully effective treatments and result in significant morbidity.

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Article Details

VOLUME: 14
ISSUE: 12
Page: [1463 - 1468]
Pages: 6
DOI: 10.2174/1568026614666140523115732