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PEPTIDE TRENDS MARCH 2018

MEET US AT IN-COSMETICS GLOBAL

In-cosmetics global is the leading global event for personal care cosmetic ingredients and the launch place for innovation in ingredients and technologies, providing high-level scientific education and consumer insights for formulators, R&D and regulatory professionals. The 2018 edition will take place on April 17th – 19th at RAI Amsterdam, The Netherlands.

 

Peptides as ingredients in cosmetic products, most notably in anti-aging therapy, are of continued interest. Due to our offer for cosmeceutical-related products, our excellent service for custom peptide synthesis, and our capabilities for small to industrial scale synthesis of peptides of any complexity we are confident to be the ideal partner in the development and production of cosmetic peptides.

 

We are excited to meet with our customers at this part of the world and discuss how Bachem can help with their cosmetic peptide needs. We invite you to visit us at our Booth M320: please contact us to schedule a meeting in advance.

 

We look forward to meeting you at in-cosmetics global 2018!

PEPTIDES IN COSMETICS

Peptides are involved in many physiological processes. Their broad acceptance as natural molecules, relatively high stability and well-defined actions make them attractive for many skin-related indications, most notably in anti-aging therapy. We have considerable expertise and long-standing experience in peptide synthesis. With our capacity to upscale the production of simple and modified peptides, we are the partner of choice for the pharmaceutical and cosmetic industries. Our portfolio reaches from catalog products, which can be purchased in small amounts for research, to the production of commercial batch sizes used by our customers for formulation. In addition, we offer several services such as the assurance of the compatibility with CMR requirements and microbiological limits.

Custom Synthesis and Support

Custom Synthesis at Bachem  
Quality
- GMP and non-GMP quality
- Broad range of purities
- State of the art analytical capabilities
- ISO 13485 certified manufacturing sites in Vista, U.S. and St. Helens, United Kingdom
 
Chemistry
- Fmoc-, Boc-, Z- and other synthetic strategies
- Native chemical ligation
- Synthesis of complex peptides
 
Capacity
- Production sites in the USA and Europe
- Largest production facilities in the market
- Up-to-date technology
 
Modifications
- Acylation, acetylation, amidation, etc.
- Cyclizations
- Stabilizing modifications
 
Support
- Highly qualified technical support team
- Documentation
- Confidentiality
 
Step in Project Performed by
Catalog products (small amounts, mostly from stock) for early research Bachem
R&D, discovery of new peptide cosmetic ingredients Our customers
Handling of intellectual properties on the active ingredients Our customers
Synthesis of the first proof of concept batch for early development Bachem
Formulation development Our customers
Early tests on mode of action and dosage Our customers
Process development for scale-up till the commercial batch size Bachem
Compatibility with CMR requirements (residual solvent, heavy metal traces) Bachem
Compatibility with microbiological limits Bachem
Toxicological studies Our customers
INCI registration Our customers
Production of commercial peptide batches Bachem

Peptides in Cosmetics

Peptides have become very important ingredients in cosmetic products. According to their mode of action, they have been divided into three main groups: signal peptides, neurotransmitter-affecting peptides, and carrier peptides. The first group mainly consists of peptides which are able to increase collagen synthesis, or alternatively, inhibit the breakdown of collagen by collagenase. The second group includes peptides mimicking the effects of botulinum neurotoxins whereas the third group, the carrier peptides, acts by delivering trace elements required for enzymatic processes.

 

Signal peptides

Aged skin is, amongst others, characterized by reduced levels of collagen and elastin. Increasing the number of fibroblasts or their collagen production and/or inhibiting further collagen hydrolysis are therefore considered effective means to halt or slow the aging process of the skin. Many of the peptides used in cosmetic preparations are compounds which act on fibroblasts. One of the peptides described to act in this way is H-Val- Gly-Val-Ala-Pro-Gly-OH (VGVAPG) (Product: H-2390 Chemotactic Domain of Elastin). H-2390 is an elastin-derived peptide sequence repeated several times in tropoelastin. It was found to stimulate the proliferation of human skin fibroblasts presumably via the elastin receptor. The N-terminally palmitoylated peptide is marketed under the name of palmitoyl-oligopeptide and is supposed to penetrate more efficiently through the epidermis than the parent compound. H-Lys-Thr-Thr-Lys-Ser-OH (KTTKS) (Product: H-1592 Procollagen Type I (212-216)) is a subfragment of the carboxy-terminal propeptide of type I collagen (residues 197-241) and represents the minimal sequence shown to stimulate extracellular matrix biosynthesis in fibroblasts. It augments type I and II collagen and fibronectin production in a dose- and time-dependent manner with no effect on total protein synthesis or on the ratio of secreted proteins to cell-associated proteins. The N-terminally palmitoylated peptide is marketed as a cosmetic ingredient under the designation palmitoyl pentapeptide-3.

 

Neurotransmitter-affecting peptides

Many of the peptides used in cosmetic preparations belong to the group of neurotransmitter-affecting peptides. These peptides act in a similar way as botulinum toxin (Botox). By inhibiting signal transduction pathways at neuromuscular junctions they attenuate the formation of wrinkles and fine lines which appear over time due to the repetitive contraction of the intrinsic muscles of facial expression. A well-known mimic of botulinum toxin used in cosmetic preparations is Acetyl-Glu-Glu-Met-Gln-Arg-Arg-NH2. It is a synthetic peptide corresponding to a sequence within the N-terminal region of SNAP-25 (amino acids 12-17) and competes with SNAP-25 for a position in the SNARE complex, thereby modulating its formation. The resulting destabilization of the SNARE complex leads to an inhibition of neurotransmitter release and a subsequent attenuation of muscle contraction. Another class of potentially interesting substances in the cosmetic industry includes peptides derived from snake venoms. Waglerin-1 (H-Gly-Gly-Lys-Pro-Asp-Leu- Arg-Pro-Cys-His-Pro-Pro-Cys-His-Tyr-Ile-Pro-Arg-Pro-Lys-Pro-Arg-OH), for example, is a peptide isolated from the venom of the temple viper, Tropidolaemus wagleri. It consists of 22 amino acids and selectively blocks the epsilon form of the muscular nicotinic acetylcholine receptor (mnAChR) thereby keeping the affected muscles in a relaxed state.

 

Carrier peptides

The tripeptide H-Gly-His-Lys-OH (GHK) (Product: H-3510 Liver Cell Growth Factor) was originally identified in human plasma and has a high affinity for copper2+ (Cu2+). It acts as a signaling peptide and a carrier molecule for copper which is a co-factor for several enzymes involved in collagen and elastin formation. The copper peptide was shown to stimulate wound healing but also to reduce fine lines and wrinkles and to improve elasticity and firmness of aged skin. A wide variety of effects have been ascribed to GHK-Cu. The peptide exhibits anti-inflammatory actions by suppressing the expression of pro-inflammatory cytokines. It also chemoattracts capillary cells, macrophages and mast cells, increases the synthesis of collagen and elastin, and stimulates the proliferation of fibroblasts and keratinocytes.

 

Other mechanisms

Many peptides used in cosmetic preparations act by other mechanisms to improve skin appearance or delay skin aging. These include ROS scavengers, collagen fiber organizing compounds, and anti-inflammatory peptides: Peptides such as carnosine (Product: G-1250), anserine (Product: G-4555 L-Anserine · nitrate) and carcinine (Product: G-4425) are histidine dipepeptides with antioxidant activity.

 

Conclusions

Synthetic peptides have become important for the cosmetic industry. Due to demographic changes and the aging population wishing to maintain a young lifestyle and appearance, cosmetic industry research has focused on anti-aging skin therapy. Today, more than 30 peptides are used in anti-aging skin care products and there are many more in development. Bachem is the market leader in the production of synthetic peptides and has long standing partnerships with major firms in the pharmaceutical and cosmetic industry. We are well-equipped for small to industrial scale synthesis of peptides of any complexity. Bachem is therefore the ideal partner in the development and production of cosmetic peptides. Together with our customers, we accomplish each of the demanding steps in a development project, finally leading to the successful cosmetic product.

 

References

Product Monograph Peptides in Cosmetics

 

Please explore our broad offering of Cosmetic Peptides & Dermatology Research Products

PEPTIDES IN CLINICAL DEVELOPMENT FOR DERMATOLOGY APPLICATIONS

Peptides are emerging as new therapeutic tools for a wide range of applications in the field of dermatology. Some peptides affect various cellular and molecular processes within the skin through modulation of collagen, elastin and melanin. In particular, the ability of some synthetic peptides to increase or maintain production of dermal extracellular matrix proteins such as collagen is of interest for anti-aging applications (1). Furthermore, researchers have shown that several peptides have the ability to promote wound healing, cell migration and angiogenesis. As shown in Table 1, there are many peptides in various clinical phases of development for the treatment of a variety of dermatologic conditions such as acne, dermatitis, ulcers and psoriasis.

Table 1 Peptides for Dermatology in Phase I to III clinical trials and pending approval

Product Name Active Ingredient Condition Treated Highest Phase Company Name
Xylentra -- Burn Scar(PA) Pending Approval Issar Pharmaceuticals Pvt Ltd
CLS001 omiganan pentahydrochloride Papulopustular Rosacea(III), Acne Vulgaris(II), Atopic Dermatitis(II), Dermatology(II), Genital Warts(II) III Cadence Pharmaceuticals Inc, Fujisawa Pharmaceutical Co., Ltd., Cutanea Life Sciences Inc, BIOWEST THERAPEUTICS Inc., Maruho Co Ltd
Demegel D2A21 Wound(III), Trichomoniasis(PC) III Demegen Inc
ANP017 -- Diabetic Foot Ulcer(II) II ANP Technologies Inc
DPK060 -- Atopic Dermatitis(II), Otitis Externa(II) II DermaGen AB, Transdermal Therapeutics, Promore Pharma
LL37 -- Varicose Ulcer(II) II Promore Pharma, APL, PharmaResearch Products Co Ltd, PCG Clinical Services
CB-0601 -- Acne(II) II Naicons Laboratories, KtedoGen, Cassiopea SpA
P144 disitertide Scleroderma(II), Systemic Sclerosis(II), Actinic Keratosis(I), Psoriasis(I), Skin Cancer(I), Age-Related Macular Degeneration(PC), Burns(PC), Cardiovascular(PC), Coronary Artery Diseases(PC), Dermal Surgery(PC), Idiopathic Pulmonary Fibrosis(PC), Keloid Scar(PC), Keratoconjunctivitis Sicca(PC), Liver Fibrosis(PC), Melanoma(PC), Peritoneal Dialysis(PC), Ulcerative Keratitis(PC) II Digna Biotech SL, Avadel Pharmaceuticals Plc, ISDIN, Flamel Technologies SA, Aachen Resonance Holding AG
RGN-137 thymosin beta4 Epidermolysis Bullosa(II), Pressure Ulcers(II), Venous Stasis Ulcers(II), Burns(PC), Diabetic Foot Ulcer(PC) III (planned) GtreeBNT
SR0379 -- Skin Ulcers(II) II Osaka University, AnGes Inc, FunPep Co Ltd, Shionogi & Co Ltd
BBI2000 -- Dermatitis(I) I Syngenta AG, Brickell Biotech Inc, The University of Manchester
ShK186 dalazatide Autoimmune Disorders(I), Dermatology(I), Antineutrophil Cytoplasmic Antibodies Associated Vasculitis(PC), Asthma(PC), Autoimmune Arthritis(PC), Inflammatory Bowel Disease(PC), Insulin-Dependent Diabetes Mellitus(PC), Lupus Nephritis(PC), Obesity(PC) I University of California, Irvine, KPI Therapeutics, Seattle Children's Research Institute, Baylor College of Medicine, University Medical Center Groningen, Debiopharm Group, Kv1.3 Therapeutics, Airmid Incorporated

Pending Approval

XylentraTM, an antimicrobial peptide, is under development by Issar Pharmaceuticals for the treatment of burns to control infection, accelerate wound healing and prevent scaring. Issar has submitted an application to the Indian regulatory authority, Central Drugs Standard Control Organization, for the approval of Xylentra (2).

 

Phase III Candidates

Another antimicrobial peptide, CLS001 (omiganan pentahydrochloride), is under development by Cutanea Life Sciences for the treatment of several indications including papulopustular rosacea, vulvar intraepithelial neoplasia, inflammatory papules, genital warts, acne vulgaris and atopic dermatitis. This drug candidate is currently in a Phase III study for the treatment of rosacea to evaluate the safety and efficacy of once-daily CLS001 (2).

 

Demegen is developing Demegel for the treatment and prevention of burn or wound infection and Trichomonas vaginalis infection. This antimicrobial peptide acts against multi-drug resistant strains of Pseudomonas aeruginosa and Staphylococcus aureus and the peptide exhibits antifungal activity. Demegel is under evaluation in a Phase III clinical trial for burn wounds (2).

 

Phase II Candidates

ANP017 is under development by ANP Technologies for the treatment of diabetic foot ulcers. This peptide-based drug candidate targets the protective receptor of a key biological pathway (2). ANP-017 is currently in a Phase II clinical study (3).

 

Transdermal Therapeutic Technologies LLC is developing DPK060, an antimicrobial peptide, for the treatment of atopic dermatitis and acute external otitis. In 2017, Transdermal Therapeutic Technologies entered into an exclusive worldwide licensing agreement with Promore Pharma, formerly Pergamum AB, to develop and commercialize DPK-060. In addition, DPK060 was part of the EU-funded FORMAMP project, an initiative to develop stable nano-formulations of antimicrobial peptides for treating infectious diseases. As a result, DPK060 was incorporated into a nanoparticle pharmaceutical preparation with improved efficacy (3).

 

LL37 is an antimicrobial peptide under development by Promore Pharma for the treatment of venous leg ulcers. This peptide is derived from the C-terminus of human cathelicidin (hCAP-18) and it modulates inflammation, prevents apoptosis, promotes wound healing, cell migration and angiogenesis (2). In 2018, Promore Pharma is planning to commence a phase II trial of LL37 in patients with venous leg ulcers (3).

 

CB-0601, a semi-synthetic thiopeptide, is under development by Cassiopea SpA for the treatment of acne. The peptide is selective against Propionibacterium acnes including antibiotic-resistant strains. In 2016, Cassiopea completed a Phase II proof of concept trial of CB-0601 in patients with moderate to severe acne. Results from the study suggested that CB-0601 could potentially be an efficacious treatment for acne (3).

 

Digna Biotech SL is developing P144 for the treatment of a range of indications including scleroderma, systemic sclerosis, actinic keratosis, skin cancer and psoriasis. P144 contains disitertide, a 14-mer fragment (730–743) of human Transforming growth factor-β receptor III (betaglycan) that acts by binding and inhibiting transforming growth factor beta-1 (TGF-β1). TGF-β1 is responsible for biological activities such as cellular proliferation, immunomodulation, angiogenesis and fibrogenesis (2). Flamel Technologies SA and Digna Biotech were jointly developing P144 using Flamel’s Medusa and micropump drug delivery technologies; however, this partnership was terminated in 2013 (3).

 

RGN-137, a Thymosin β-4 (Tβ4) drug candidate which was developed by RegeneRx for the treatment of burns, diabetic foot ulcers, epidermolysis bullosa, pressure ulcers and skin ulcers is currently being developed by GtreeBNT after the execution of the license agreement between the two companies in 2014. RGN-137 is a topical gel formulation of Tβ4 (4). Preclinical studies have demonstrated that RGN-137 affects several healing pathways including apoptosis, angiogenesis, collagen deposition and tissue inflammation. In 2017, GtreeBNT received permission from the U.S. Food and Drug Administration to start a Phase III trial of RGN-137 for the treatment of epidermolysis bullosa (2).

 

SR0379 is under development by Shionogi & Co., Ltd for the treatment of skin ulcers. This 20-mer synthetic peptide targets the Phosphoinositide 3-Kinase/Akt/Mammalian Target of Rapamycin Signaling (PI3 kinase-Akt-mTOR) pathway (2). By activating this pathway, it increases epithelial cell proliferation, cell migration, and wound healing. SR0379 also exhibits antibacterial activity. In 2017, Osaka University initiated a Phase II trial of SR0379 to evaluate the safety and efficacy of SR0379 in Werner syndrome patients who have limb ulcers (3).

 

Phase I Candidates

Brickell Biotech is developing BBI2000, an anti-inflammatory peptide derived from thioredoxin. The company is developing this drug candidate for the treatment of dermatitis. In 2017, Brickell Biotech completed a Phase I study of BBI2000 to evaluate the effect of BBI2000 on allergic responses in patients with contact hypersensitivity to diphencyprone (2).

 

Dalazatide is under development by Kv1.3 Therapeutics for several indications including inclusion body myositis (IBM) and other rare and autoimmune diseases including skin diseases such as cutaneous lupus, plaque psoriasis and atopic dermatitis. Dalazatide is a 37-amino acid cyclic peptide toxin that was originally isolated from the sea anemone, Stichodactyla helianthus (2). The drug candidate is ready to begin Phase II clinical trials for IBM (5).

 

Conclusion

Peptides have numerous potential applications in the field of dermatology. For researchers and organizations developing peptides for dermatologic uses, Bachem offers a selection of cosmetic and dermatology peptides. In addition, Bachem offers a comprehensive custom peptide synthesis service and the production of new chemical entities to assist companies with developing peptide-based therapeutics.

 

References

(1) B. Reddy et al., Bioactive oligopeptides in dermatology: Part I. Experimental Dermatology. 21(8), 1600-1625.

(2) Medtrack (2018)

(3) GlobalData (2018)

(4) RGN-137, RegeneRx, (2017)

(5) Dalazatide, Kv1.3 Therapeutics (2017)

MEET BACHEM: ELISABETH MOSER, SALES REPRESENTATIVE

PT: What is your official job title at Bachem?

Elisabeth: My job title is Sales Representative

 

PT: How long have you been with Bachem? Where did you work before Bachem?

Elisabeth: I started working at Bachem in June 2012. Before joining Bachem, I worked in a watch and jewelry shop.

 

PT: Briefly, what do you do at Bachem?

Elisabeth: I am responsible for inquiries and processing of quotations and orders for our catalog products.

 

PT: What do you like to do outside of work (interests, hobbies)?

Elisabeth: I like travelling, reading, singing and spending time with my family.

 

PT: What is your business motto?

Elisabeth: Be friendly and polite to everyone and you will be treated the same way.

 

PT: What do you like most about your job?

Elisabeth: Being in contact with customers from all over the world.

 

PT: Would you like to communicate any key message to the reader?

Elisabeth: SMILE! A friendly facial expression offers many benefits. It improves your mood, opens your creativity and leads to positive encounters with other people.

 

PT: Thank you very much Elisabeth.

PEPTIDE HIGHLIGHTS

Interesting news about peptides in basic research and pharmaceutical development:

Circulating cancer cells torpedoed by peptide–chemo conjugate-Genetic Engineering & Biotechnology News

Breakthrough for peptide medication-Technical University of Munich

Study suggests new strategy against vascular disease in diabetes-EurekAlert!

U of T scientists create mirror-image molecules to develop better medicines-University of Toronto

LITERATURE CITATIONS

Bachem peptides and biochemicals are widely cited in research publications. Congratulations to all our customers with recent publications!

 

O. Abdelhedi et al.

Collagenous proteins from black-barred halfbeak skin as a source of gelatin and bioactive peptides.

Food Hydrocolloids 70, 123-133 (2017)

 

C. Holz et al.

Novel bioactive from Lactobacillus brevis DSM17250 to stimulate the growth of Staphylococcus epidermidis: a pilot study.

Beneficial Microbes 8, 121-131 (2017)

 

I.P. Moreira et al.

Biocatalytic self-assembly of tripeptide gels and emulsions.

Langmuir 33, 4986-4995 (2017)

 

M. Yazaki et al.

Oral ingestion of collagen hydrolysate leads to the transportation of highly concentrated Gly-Pro-Hyp and its hydrolyzed form of Pro-Hyp into the bloodstream and skin.

Journal of Agricultural and Food Chemistry 65, 2315-2322 (2017)