Ann Dermatol.  2016 Oct;28(5):555-561. 10.5021/ad.2016.28.5.555.

Kojic Acid Peptide: A New Compound with Anti-Tyrosinase Potential

• Singh BK
• Park SH
• Lee HB
• Goo YA
• Kim HS
• Cho SH
• Lee JH
• Ahn GW
• Kim JP
• Kang SM
• Kim EK

• KMID: 2382878
• DOI: http://doi.org/10.5021/ad.2016.28.5.555

Abstract

BACKGROUND
Kojic acid was used for decades in the cosmetic industry as an antimelanogenic agent. However, there are two major drawbacks of Kojic acid, one is cytotoxicity and second are instability on storage. These limitations led the scientist to synthesize the active Kojic acid peptides.
OBJECTIVE
In the present study, we synthesize and investigate the effect of five Kojic acid peptides to overcome the limitation of Kojic acid.
METHODS
The peptide was analyzed and purified by high-performance liquid chromatography and matrix-assisted laser desorption ionization time of flight mass spectroscopy. Further, the tyrosinase activities of the Kojic acid and Kojic acid peptides were compared. The toxicity was measured and the melanin content is recorded in B16F10 mouse melanoma cells.
RESULTS
Maximum tyrosinase activity was measured by Kojic acid peptides. Therefore, Kojic acid peptides were subjected to melanin assay and cytotoxicity assay and finally the stability of the Kojic acid peptide was measured.
CONCLUSION
It was observed that this newly synthesized Kojic acid peptide is stable and potent to inhibit the tyrosinase activity and melanin content of B16F10 mouse melanoma cells without exhibiting cell toxicity. Together, these preliminary results suggest that a further exploration is being needed to establish Kojic acid peptide as antimelanogenic agent.

Keyword

Hypopgmentation; Kojic acid; Melanin; Peptides; Tyrosinase

MeSH Terms

Animals
Chromatography, Liquid
Mass Spectrometry
Melanins
Melanoma
Mice
Monophenol Monooxygenase
Peptides
Melanins
Monophenol Monooxygenase
Peptides

Figure

• 

  Fig. 1 Synthesis of activated Kojic acid by using 1,1-carbonyldiimidazole (CDI) at room temperature.

• 

  Fig. 2 Synthesis of Kojic acid peptides (KA-peptides). Reagents and conditions; a) Treat with 2% 1,8-diazabicyclo[5.4.0]undec-7-ene in N,N'-dimethylformamide (DMF) for 10 min; b) Mixed Fomc-A.A2-OH (5.0 equivalent [eq.]), hydroxybenzotriazole (HOBt) (5.0 eq.), and diisopropylcarbodiimide (5.0 eq.) with resin for 2 hours; c) repeat a) and b) procedure; d) React with KA-imidazole (3.0 eq.), HOBt (3.0 eq.) in DMF for overnight; e) React with reagent K. [trifluoroacetic acid/thioanisole/phenol/water/ethanedithiol (82.5/5/5/5/2.5(v/v)] for 1 hour, and treat with pre-cooled diethylether.

• 

  Fig. 3 Screening of newly synthesized Kojic acid peptides (KA-PKEK, KA-ECG, KA-CR9, KA-KECG, and KA-PS) through the invitro tyrosinase assay. Data are mean±standard deviation. **p<0.001; t-test.

• 

  Fig. 4 Showing the dose dependent decrease in the mushroom tyrosinase activity by KA-CR-9. Data are mean±standard deviation. *p<0.05, **p<0.001, ***p<0.0001; t-test.

• 

  Fig. 5 Showing the dose dependent inhibition of the mushroom tyrosinase activity by KA-PS. Data are mean±standard deviation. *p<0.05, **p<0.001, ***p<0.0001; t-test.

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  Fig. 6 B16F10 melanoma cell and melan-a cells were cultured in the presence of Roswell Park Memorial Institute media supplemented with 10 fetal bovine serum. Arbutin and KA-PS acid inhibited melanin content of α-melanocyte-stimulating hormone (10 nM) induced B16F10 melanoma cells (A) and melan-a cells (B). Melanin content and cell viability (% of control) in both B16F10 cells (A) and melan-a melanocytes (B) are shown. Data are mean±standard deviation. *p<0.05, **p<0.001; t-test.

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