R006E

Mimosine, a non-proteinogenic amino acid, Mimosinederivatives for Mimosyl-peptides
Mimosine, useful functional ingredientsfor development of pharmaceuticals/
cosmeceuticals:

Hydroxyketones OHOH

Derivatives containing hydroxyketone, which is involved in Mimosine(Mim) are attracted by their anti-tumor effects and apoptosis inducing
effects. Mim has the tyrosinase, cycloxygenase and lipoxygenase
inhibitory activities and thus for whitening big in the cosmetic field is
one of the big interests. Mim exhibits no significant cytotoxicity nor
acute dermal toxicity. A large scale extraction, purification, physicochemical characterization of high quality Mimosine from plantLeucaena leucocephala de Wit has been established by HiPep
Lqboratories as a sustainable starting material for development ofdrugs or cosmetics, without causing environmental damages. Opticalpurity has been assessed by the novel method (*A part of those work
was funded by the Regional Resource Utilization R&D Programs:
Ministry of Economy, Trade and Industry, Okinawa General Bureau
2007-8. HiPep Laboratories has also established production ofMimosyl-peptides for functional cosmetics or active pharmaceuticalingredients. Reagent for peptide syntheses are commercialized.

ONNH2O

2-amino-3-(3-hydroxy-4-oxo-4Hpyridin-1-yl)-propionic acidmV90 検出器A:254nm

D-Mim

8070

L-Mim

6050403020100

Products from HiPep Laboratories
Mimosine (Mim) with high optical purity) is a plantderived non-proteinogenic amino acid; further FmocMim, Mim-resin (for SPPS), Mim-CTCResin areavailable for the syntheses of Mimosyl-peptides.
Mim-Peptides have antioxidant, whitening activities.

0.0

2.5

5.0

7.5

10.0

12.5

15.0

17.520.0

22.5

25.0

27.5

Fmoc-Mimosinewith MSDS

History of the Okinawa Project
2004-2006

Okinawa Bio Project was started and HiPep-Okinawa Lab wasfounded. Fundamental technologies for molecular design,
library construction, highly efficient library construction,
synthesis and purification have been carried out in Okinawa.

2007-2008

Manufacturing unnatural amino acid Mimosine as an unique
resource of Okinawa as started. Efficient production method
has been established, that is purification of industrial scale ofhigh quarity Mimosine from natural (plant) Leucaena
leucocephala, was succeeded.

2011

After 3 years of “Innovation R&D Project” focusing on
diagnostics and theranostics, HiPep Okinawa Laboratory wasclosed, although HiPep continues looking for business
partners not only domestic but also world wide market.

Mimosyl Chlorotrityl Chloride-Resin（Mim-CTCResin) with MSDSOOHO ClONNH2References
Nokihara, K, et.al., Amino Acids (2012) 54, 27-36.
Nokihara, K, et.al., Peptide Science 2010, Japanese. Peptide Society, (2011) p 282.
HiPep Laboratories Nakatsukasa-cho 486-46, Kamigyo-ku, Kyoto, 602-8158, Japan
TEL: 075-813-2101, FAX: 075-801-0280, E-mail: info@hipep.jp, URL: http://www.hipep.jp/

1minR006E

Mimosine, a non-proteinogenic amino acid, Mimosinederivatives for Mimosyl-peptides
Mim showed no-toxicities,
Evaluation Skin irritation showed SAFE
(Patch test + Usage Test) = Itch, Erythema, Eczema,
Scaliness, Acne (all Negative)

Melanocyte

Tyrosine
Tyrosinase
Efficacy of Mimosyl-peptides

MelanineCosme.

Drug

SanitaryFood◯◯

1

Anti-oxidant◯◯2αMSH antagonist◯◯

List of Safetytest

Patch test5 volunteers）

3Whitening◯

4

Anti-viral◯

Itch0/55

Anti-tumorErythema

0/5

6Anti-bacterial

Eczema0/5

7Anti-angiogenesis◯Scaliness

0/5

8Anti-inflammatory

◯

Acne

0/5

9

Treatment of alopecia

10Fat suppression◯◯◯◯◯◯◯◯

Topic: Immunopotentiation by"L-Mimosine" and prevention of invasive Candida infection
UT Southwestern Medical Center group (Texas, USA) found that immunomodulation by administration of "L-Mimosine (Mim)"and Mim could be useful for treatment for invasive cancer infections.

Candida is a type of mold normally inhabiting human skin and intestines, usually occurring in the skin, mouth, in the woman‘svagina, half of those who have internal Candida. Normally it is harmless but Candida increases too much and if it leaks from theinternal organs to the blood, it becomes “invasive Candida infection” and the mortality rate is about 30%. There are antibiotics
against serious invasive Candida infections, but it is not always effective. Even those with durability in medicine are also
occurring in the first place. The research group noticed that bacteria (especially intestinal bacteria) present in the internalorgans constrained the proliferation of Candida and administered “Mim" to Candida infected rats and verified it.
"Mim" is known to enhance the activity of the transcription factor HIF-1α. As a result of the experiment, it was found that "HIF1α" made LL-37, a natural antibiotic, built in the internal organs and suppressed Candida to 1/100. The approach of boosting
the immune system of the bowel and reducing Candida may be a novel treatment to prevent invasive infections.
References
Boosting gut bacteria defense system may lead to better treatments for bloodstream infections, study shows
Fan D et al. Activation of HIF-1α and LL-37 by commensal bacteria inhibits Candida albicans colonization. Nat Med. 2015 Jun 8.
Activation of HIF-1α and LL-37 by commensal bacteria inhibits Candida albicans colonization. – PubMed – NCBI ”
title=”Activation of HIF-1α and LL-37 by commensal bacteria inhibits Candida albicans colonization. – PubMed – NCBI Nat Med.
2015 Jul;21(7):808-14.

HiPep Laboratories Nakatsukasa-cho 486-46, Kamigyo-ku, Kyoto, 602-8158, Japan
TEL: 075-813-2101, FAX: 075-801-0280, E-mail: info@hipep.jp, URL: http://www.hipep.jp/2