Proteins, Peptides
Proteins, Peptides, and the Hidden Logic of Sequence → Structure → Function
From amino-acid strings to 3D folds, motifs, and consumer-grade bioactive peptides. A practical guide for R&D and OEM formulators.
1) What are Proteins & Peptides?
Proteins are long polymers of amino acids (typically 100–1000+ aa) that fold into complex 3D shapes. Peptides are shorter fragments (2–50 aa common in cosmetics/biotech) that can mimic a tiny “message” of a large protein—often safer, cheaper, and easier to formulate.
- Peptide bond: carboxyl (–COOH) + amine (–NH₂) → –CO–NH– linkage (condensation).
- Backbone torsions: φ/ψ angles control local shapes (α-helix, β-sheet, turns).
- Side chains: charge/hydrophobicity drive packing, interfaces, and receptor binding.
2) The Four Levels of Structure
- Primary – linear sequence (e.g., GHK, KTTKS). Proteases “read” this level.
- Secondary – local motifs: α-helix, β-sheet, β-hairpin, PPII helix.
- Tertiary – full 3D fold via hydrophobic packing, salt bridges, H-bonds, disulfides.
- Quaternary – multi-chain assemblies (collagen triple helix, hemoglobin tetramer).
Rule of thumb: sequence encodes propensities; environment (pH, ions, cosolvents, membranes) “chooses” the actual fold or interface.
3) Sequence Design Cheatsheet (SAR)
| Design lever | Effect on Function/Formulation | Notes |
|---|---|---|
| Charge (K/R, D/E, H) | Target binding, cell/matrix affinity, solubility | Too cationic (≥ +4) may raise irritation/hemolysis risk. |
| Hydrophobic residues (L/I/V/F/W/Y) | Membrane interaction, helix stabilization | Amphipathic helices drive penetration—but watch irritation. |
| Gly/Pro content | Turns/loops; random coil; collagen-like motifs | Pro disrupts helices; Gly enables tight turns. |
| Terminal caps (Ac– / –NH₂) | Protease resistance, charge tuning, taste/odor reduction | Common in cosmetic peptides (Acetyl-, Amide). |
| Lipidation (e.g., Palmitoyl–) | Stratum-corneum affinity, residence time | Used in Palmitoyl tripeptides/tetrapeptides. |
| D-amino acids / Cyclization | Protease resistance, conformational bias | Check activity retention; monitor safety. |
4) Motifs, Domains & Why Tiny Fragments Work
- Motifs are short recurring patterns (e.g.,
RGDbinds integrins;KTTKSfrom procollagen). - Domains are ~50–200 aa modules that fold semi-independently (e.g., SH3, Kringle). Peptides often mimic a domain’s “hotspot”.
- PTMs (post-translational mods): phosphorylation, glycosylation, disulfides—sometimes emulated by chemical tricks (lipidation, acetylation).
Examples (one-letter code)
• RGD – minimal integrin-binding motif (cell adhesion)
• GHK – Gly-His-Lys; Cu(II) chelation (tissue remodeling signal)
• KTTKS – Procollagen fragment; in Palmitoyl-Tripeptide-1 (Pal-GHK) it becomes lipidated for delivery
• GQPR – Tetrapeptide used in Palmitoyl-Tetrapeptide-7 (anti-inflammatory signaling)
5) Peptides You’ll See in Real Formulas
| INCI / Alias | Canonical/Typical Sequence | Formulation Notes | Typical Active% |
|---|---|---|---|
| Acetyl Hexapeptide-8 (Argireline) | Ac-Glu-Glu-Met-Gln-Arg-Arg-NH₂ (vendor-defined hexapeptide) |
Neuropeptide; supports expression line relaxation; water-soluble; pH ~5–7. | 0.3–1.0 (active) |
| Palmitoyl Tripeptide-1 (Pal-GHK; Matrixyl®) | Pal-Gly-His-Lys |
Collagen signal fragment with lipid tail for delivery. | 0.05–0.3 |
| Palmitoyl Tetrapeptide-7 | Pal-Gly-Gln-Pro-Arg |
Inflammation-modulating signal; pairs with Pal-GHK. | 0.05–0.3 |
| Copper Tripeptide-1 (GHK-Cu) | Gly-His-Lys·Cu²⁺ |
Chelates Cu²⁺; tissue-remodeling signals; use chelators carefully. | 0.01–0.1 |
| Oligopeptide-1 (EGF analogue) | Vendor-specific; short EGF-mimetic fragments | Often encapsulated (liposome/niosomes); low %. | ppm–0.01 |
Note: Sequences above represent common/typical forms; trade variants exist. Follow supplier tech sheets.
6) Stability, Cleavage Sites & Delivery
- Proteases: Trypsin cuts after K/R; Chymotrypsin after F/Y/W/L. Avoid easy motifs or protect them (Ac-/-NH₂ caps, D-aa, cyclization).
- pH window: Most cosmetic peptides prefer pH ~5–7. Outside this, hydrolysis/oxidation or irritation risk rises.
- Metal ions: Cu²⁺/Fe²⁺ can catalyze oxidation; add EDTA 0.05–0.1% if compatible.
- Encapsulation: Liposomes (lecithin 3–5%), niosomes, polymeric vesicles improve penetration and stability.
- Lipidation: Palmitoyl tails increase corneum affinity and residence time, enabling lower actives.
Practical guardrails (aqueous serums)
• Total active peptide load: ≤ ~1% (sensitive-skin friendly)
• Preservative: Phenoxyethanol 0.6–0.8% + Ethylhexylglycerin 0.2–0.4%
• Buffer: Citrate to pH 5.2–5.8; add EDTA if metal-sensitive actives present
• QC: 40°C/75%RH & 4°C cycling, 4–8 weeks; pH/viscosity/odor/color/micro
7) Educational Sequence Cards
• Palmitoyl-Tripeptide-1 (Pal-GHK): Pal-G-H-K
- collagen signal; lipid tail for delivery; pair with Pal-Tetrapeptide-7.
• Palmitoyl-Tetrapeptide-7: Pal-G-Q-P-R
- inflammation-modulating; synergy with Pal-GHK.
• Acetyl-Hexapeptide-8 (Argireline): Ac-X₆ (vendor-defined hexapeptide targeting SNAP-25 complex)
- expression line support; water-soluble; pH ~5–7.
• GHK-Cu: G-H-K·Cu²⁺
- copper-chelating tripeptide; signal of tissue renewal.
8) Safety, Claims & Compliance (Quick View)
- Cosmetic claims should be framed as “helps/supports the appearance of…” unless clinical data justify stronger language.
- Patch testing is essential. Keep fragrances minimal in peptide serums.
- Observe regional regulations (INCI labeling, preservative limits, heavy metals, microbial limits).
9) ZIN2 System: Beyond Conventional Compound Analysis
Our pipeline evaluates sequence features (charge, motifs, protease sites), delivery flags (lipidation/encapsulation), and stability fences (pH/metal/light), then proposes upgrade paths: palmitoylation vs. liposome, terminal caps, partial D-substitution, or cyclization—always paired with TrustProof™ checklists.
🤝 OEM Collaboration
We translate sequence-level insights into ready-to-make formulas (serums, gels, masks). Ask for Pal-GHK/Pal-GQPR bundles, Argireline blends, or GHK-Cu liposomal variants.
👉 Contact R&D / OEM
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