Dipeptide Diaminobutyroyl Benzylamide
Dipeptide Diaminobutyroyl Benzylamide is the active ingredient in SYN-AKE, a synthetic peptide mimicking waglerin-1 from temple viper venom that acts as a reversible antagonist at the muscular nicotinic acetylcholine receptor.
Dipeptide Diaminobutyroyl Benzylamide is the INCI name for the active compound in SYN-AKE, a biomimetic peptide developed by Pentapharm (now DSM). The molecule is a synthetic dipeptide designed to replicate the pharmacophoric region of waglerin-1, a 22-amino-acid neurotoxin from the Temple Viper (Tropidolaemus wagleri).
Overview
The development of Dipeptide Diaminobutyroyl Benzylamide represents a structure-activity-guided approach to cosmetic peptide design. Pentapharm researchers analyzed the binding pharmacophore of waglerin-1, identifying the minimal structural elements responsible for nAChR antagonism. The result was a small, stable dipeptide that retains the receptor-blocking activity of the parent toxin while being safe and suitable for topical cosmetic application.
The compound is commercially supplied as the diacetate salt (Dipeptide Diaminobutyroyl Benzylamide Diacetate) under the trade name SYN-AKE. It is used in anti-aging serums, creams, and targeted treatment products at typical concentrations of 1-4% of commercial solution. The dipeptide's small size and modified terminal groups (diaminobutyroyl and benzylamide) contribute to its stability and skin penetration characteristics.
Mechanism of Action
Dipeptide Diaminobutyroyl Benzylamide acts at the postsynaptic side of the neuromuscular junction, distinguishing it from presynaptic-acting peptides like Argireline and SNAP-8. The mechanism involves:
- Competitive binding: The dipeptide competes with acetylcholine for the orthosteric binding site on the muscular nAChR (alpha-1 subunit)
- Channel blockade: Receptor occupancy prevents acetylcholine-triggered ion channel opening
- Reduced endplate potential: Without sodium influx, the motor endplate potential is diminished below the threshold for action potential generation
- Attenuated muscle contraction: Facial expression muscles contract less frequently and with less force, reducing dynamic wrinkle formation
The key pharmacological distinction is selectivity: the compound preferentially targets the muscular-type nAChR (containing alpha-1 subunits found at the neuromuscular junction) over neuronal subtypes (alpha-3, alpha-4, alpha-7), which mediate cognitive and autonomic functions. This selectivity was inherited from the parent molecule waglerin-1, which evolved specifically to paralyze prey through muscular nAChR blockade Molles et al. (2002).
In muscle cell contraction assays, the compound reduced contraction frequency by up to 82% at optimal concentrations. The antagonism is fully reversible -- the effect persists only while the peptide occupies the receptor, providing an inherent self-limiting safety mechanism.
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Research
Combination with Presynaptic Peptides
Because Dipeptide Diaminobutyroyl Benzylamide targets the postsynaptic receptor while Argireline and SNAP-8 target presynaptic vesicle fusion machinery, the two approaches are mechanistically complementary. Formulations combining postsynaptic and presynaptic neuromuscular peptides may achieve additive wrinkle reduction through dual-site inhibition of neuromuscular transmission.
Formulation and Stability
The diacetate salt form provides improved water solubility and formulation stability. The compound is stable at pH 4.0-6.5 and compatible with standard cosmetic emulsion systems. The benzylamide group contributes to lipophilicity, aiding penetration through the stratum corneum. Recommended storage is at 2-8C for bulk material and room temperature for finished formulations.
Waglerin-1 Parent Molecule
Waglerin-1 is a 22-residue disulfide-bridged peptide from Tropidolaemus wagleri venom. It causes flaccid paralysis by blocking the muscular nAChR with high affinity and selectivity. Molles et al. (2002) mapped the specific residues mediating species-selective receptor binding, providing the structural blueprint for the synthetic dipeptide analog.
Clinical Anti-Wrinkle Efficacy
DSM clinical studies report that topical application of 4% SYN-AKE solution (containing Dipeptide Diaminobutyroyl Benzylamide Diacetate as active) applied twice daily for 28 days produced mean wrinkle depth reductions of 52% in the crow's feet area. Onset of visible improvement was reported within the first week in some subjects, faster than typically observed with SNARE-targeting peptides Lintner et al. (2009).
Safety Profile
Dipeptide Diaminobutyroyl Benzylamide has a favorable safety profile for topical cosmetic use. The competitive and reversible nature of nAChR antagonism provides an inherent safety margin -- effects dissipate as the peptide dissociates from the receptor. Clinical studies report no irritation, sensitization, or systemic neuromuscular effects at recommended concentrations. Topical absorption is insufficient to produce systemic receptor blockade. Standard toxicological testing (patch test, phototoxicity, Ames mutagenicity) confirms safe cosmetic use. The compound is approved for cosmetic application in the EU, US, and other major markets. No tolerance development or tachyphylaxis has been observed with prolonged use.
Pharmacokinetic Profile
- Half-life
- Not established (topical)
Quick Start
- Route
- Topical
Molecular Structure
- Formula
- C23H30N4O4 (free base)
- Weight
- 375.5 Da
- CAS
- 823202-99-9
- PubChem CID
- 59499763
- Exact Mass
- 375.2270 Da
- LogP
- -1.1
- TPSA
- 131 Ų
- H-Bond Donors
- 4
- H-Bond Acceptors
- 5
- Rotatable Bonds
- 9
- Complexity
- 508
Identifiers (SMILES, InChI)
InChI=1S/C19H29N5O3/c20-10-8-15(18(26)22-13-14-5-2-1-3-6-14)23-19(27)16-7-4-12-24(16)17(25)9-11-21/h1-3,5-6,15-16H,4,7-13,20-21H2,(H,22,26)(H,23,27)/t15-,16-/m0/s1
CTUFKZFWHRPQEC-HOTGVXAUSA-NResearch Protocols
topical
The result was a small, stable dipeptide that retains the receptor-blocking activity of the parent toxin while being safe and suitable for topical cosmetic application. Clinical Anti-Wrinkle Efficacy DSM clinical studies report that topical application of 4% SYN-AKE solution (containing Dipeptide D
| Goal | Dose | Frequency | Duration |
|---|---|---|---|
| General Research Protocol | See literature | Twice daily | 28 days(Route: Topical) |
Interactions
Peptide Interactions
Because Dipeptide Diaminobutyroyl Benzylamide targets the postsynaptic receptor while Argireline and SNAP-8 target presynaptic vesicle fusion machinery, the two approaches are mechanistically complementary. Formulations combining postsynaptic and presynaptic neuromuscular peptides may achieve add...
Because Dipeptide Diaminobutyroyl Benzylamide targets the postsynaptic receptor while Argireline and SNAP-8 target presynaptic vesicle fusion machinery, the two approaches are mechanistically complementary.
Quality Indicators
What to look for
- Well-established safety profile
Frequently Asked Questions
References (6)
- [5]
- [6]Negari et al Peptide-based cosmeceuticals: mechanisms and clinical applications Int J Mol Sci (2023)
- [7]
- [1]Molles BE et al Identification of residues mediating species selectivity of waglerin-1 for nAChRs J Biol Chem (2002)
- [3]
- [2]Lintner K et al Cosmetic peptides Int J Cosmet Sci (2009)
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