SN-KE Peptide

Bhardwaj, Vinay, et al. Cosmetics, 2022, 9(4), 80.

In this work, two topical skin care formulations were formulated using the same active ingredients in the core technology, except that zinc salt of L-pyrrolidone carboxylic acid (Zinc-PCA) in the cream-gel was used to target oily skin. The cream-gel (n = 30) and cream (n = 33) were evaluated for the face and neck. The results showed that the potential mechanism of action of the anti-wrinkle technology could be remodeling of the dermal extracellular matrix (ECM), and both tested formulations were effective and well tolerated.
Active ingredients in the anti-wrinkle formulation
· The main actives of this anti-wrinkle cream are mainly plant extracts, peptides, and encapsulated hyaluronic acid. The double aim to target wrinkles was employed in the selection of synthetic peptides - to stimulate collagen production (signal peptide) and to produce a botulinum toxin-like effect (neurotransmitter inhibitory peptide).
· Dipeptide diaminobutyryl benzylamide diacetate (SN-KE peptide, sequence: β-Ala-Pro-Dab-NHBn-2-acetate), which is a reversible antagonist of muscle nicotinic acetylcholine membrane receptors and has neurotransmitter inhibitory effects. In addition, SN-KE Peptide has shown the ability to relax facial muscles, thereby reducing expression lines.
· Moreover, a synergistic blend of two palmitoyl peptides (Pal-GHK/Palmitoyl Tripeptide-1 and Pal-GQPR/Palmitoyl Tetrapeptide-7) is added to the formula, which is a new benchmark in signal peptides that promote collagen synthesis.

Balaev, A. N., et al. Tetrahedron Letters, 2014, 55(42), 5745-5747.

Dipeptide diaminobutyroyl benzylamide diacetate (SN-KE peptide) is a muscle nicotinic acetylcholine receptor antagonist with a similar mode of action to Waglerin 1, a peptide present in the venom of the Temple's viper. Here, a five-step synthetic method was reported to synthesize SN-KE Peptide.
Synthesis steps of SN-KE peptide
· 3-Chloropropionyl chloride was dissolved in methylene chloride at -10 °C in two amounts of L-proline and the product 6 produced a 74% yeld. Without isolation, 6 was cooled to -5 °C and treated with one equivalent of pentafluorophenol (PfpOH) followed by 1.1 equivalents of DCC in methylene chloride. Stirring the mixture at 0 °C for an hour led to the isolation of target compound 2, contaminated with N-(3-pentafluorophenoxypropanoyl)proline (8) (92:8). Pure 2 was obtained as large colorless crystals in a 56% yield after crystallization from Et2O-hexane.
· Combining L-glutamic acid 5-methyl ester with pentafluorophenyl ester 2 according to standard peptide synthesis using NMM in methylene chloride overnight in room temperature gave 81% acylated dipeptide 3.
· Subsequent treatment of dipeptide 3 with benzylamine, DCC, and HOBt in DMF at 0-5 °C afforded benzylamide 4. Optimal conditions (HOBt: 1.07 equiv, benzylamine: 1.23 equiv, DCC: 1.03 equiv, 18 h) resulted in a 69% yield of 4.
· Direct ammonolysis of the methyl ester and alkyl chloride in methanol, using excess ammonia to prevent further substitution, yielded tripeptide 5 in a 51% yield after purification by flash chromatography on silica gel (MeOH/CHCl3, 1:1).
· Finally, a Hofmann-type rearrangement, employing PIFA (1.5 equiv) in DMF-H2O (1:1) with pyridine (2.0 equiv) at room temperature for three hours, converted the -CH2C(O)NH2 group into a -CH2NH2 group.