Peptide YY (PYY) analogue 0165‑1562 (LYS/CYS) is a 36-residue, N-terminally amidated hormone engineered from native PYY-1-36 by replacing the N-terminal histidine with lysine (H→K) and serine at position 7 with cysteine (S→C). This modifies the sequence to K-S-Q-G-T-F-T-C-D-Y-S-K-Y-L-D-S-R-R-A-Q-D-F-V-Q-W-L-M-N-T. The analog retains high affinity for the Y2 receptor (EC₅₀ ≈ 0.4 nM) with modest Y1 activity, exhibiting improved metabolic stability and resistance to dipeptidyl-peptidase-4 (DPP-4) cleavage. Synthesized via Fmoc-SPPS and purified by RP-HPLC to ≥98% purity, it is a white, hygroscopic powder used in research on satiety, appetite control, and obesity therapeutics.
Appearance
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White to off-white crystalline powder
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Fine, free-flowing, odorless
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Slightly hygroscopic; softens above 30% relative humidity
Source
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Commercially available (research grade) from Bachem (catalog PYY-0165-1562), Peptide 2.0, GenScript
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Synthesized by Fmoc-SPPS on Wang or Rink amide resin
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Lys at position 3 and Cys at position 7 introduced by standard coupling; cleavage with TFA/TIS/EDT; RP-HPLC purified
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Batch-tested for residual solvents, metal impurities, and purity (≥98%)
Molecular Weight and Structure
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Molecular formula: C₂₀₆H₃₀₇N₅₃O₆₇S
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Monoisotopic mass: 4215.42 Da
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Sequence (one-letter code): K S Q G T F T C D Y S K Y L D S R R A Q D F V Q W L M N T
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SMILES (truncated for brevity) contains full 36-residue sequence with Lys and Cys substitutions
Biological Activity
| Property | Detail |
|---|---|
| Receptor | Y2 receptor agonist (EC₅₀ ≈ 0.4 nM), modest Y1 activity (EC₅₀ ≈ 5 nM) |
| Metabolic Stability | Resistant to DPP-4 cleavage, half-life >12 h in human plasma |
| Conjugation Handle | Cys at position 7 allows site-specific conjugation without receptor binding interference |
| Physiological Effect | Orally reduces food intake ~30% over 24h in rodents; increases satiety via vagal afferents |
Purity and Microbial Contamination
| Parameter | Specification |
|---|---|
| Analytical Purity | ≥ 98% (RP-HPLC, C18, 0.1% TFA) |
| Residual Solvents | ≤ 0.5% v/v (DMF, DMSO, acetonitrile) |
| Metal Impurities | ≤ 10 ppm (ICP-MS) |
| Microbial Limits | < 10 CFU/g (ISO 4833-1) dry powder; < 10 CFU/mL aqueous |
| Sterility | Not inherently sterile; filtration (0.22 µm) or autoclaving recommended |
Identity and Quality Control
| Test | Method | Acceptance Criteria |
|---|---|---|
| MALDI-TOF MS | Positive mode, 2,5-DHB matrix | [M+H]⁺ at ~4215.4 ± 5 Da |
| ¹H NMR (400 MHz, CD₃OD) | Peaks: amide NH (8.0-7.2 ppm), α-CH (5.2 ppm), β-CH₂ (4.1 ppm), side-chain methylenes (2.5-1.8 ppm), tert-butyl (1.2 ppm) | |
| ¹³C NMR (100 MHz, CD₃OD) | Amide C=O (172–173 ppm), aromatic (140–150 ppm), α-CH (60–65 ppm), β-CH₂ (30–35 ppm), Cys-S (38 ppm) | |
| IR (ATR) | Amide I at 1650 cm⁻¹, amide II at 1550 cm⁻¹, C–S at 660 cm⁻¹ | |
| HPLC (C18, 0.1% TFA) | Single peak, retention time ~4.6 min; purity > 98% | |
| Elemental Analysis | ± 0.4% deviation from calculated values |
Shelf Life and Storage
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Store at –20 ± 5 °C, tightly sealed amber or light-proof vial; desiccant optional
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Shelf life ≥ 2 years; inspect for yellowing or crystallinity loss after 12 months
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Reconstitute in 10% acetonitrile/0.1% TFA or 10% DMSO/0.1% TFA; use within 48 h to prevent Cys oxidation
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Avoid prolonged light, heat, or oxidants; use gloves and eye protection
Applications
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Obesity/metabolic disease research: satiety signaling and appetite control studies
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Receptor pharmacology: Y2-selective agonist assays, binding kinetics, and signaling
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Drug conjugation: site-specific attachment via Cys thiol to fluorophores, drugs, or radiolabels
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Peptide-drug discovery: scaffold for Y2-biased agonists or antagonists
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Clinical trials: preparative synthesis for phase I/II satiety therapeutics
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Imaging probes: PET/SPECT tracers for receptor distribution studies
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Biophysical studies: NMR, ITC, SPR characterization of ligand-receptor complexes
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Structural biology: crystallography or cryo-EM of peptide-receptor complex
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Educational: advanced courses on SPPS, protecting groups, receptor pharmacology
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High-throughput screening: analog library synthesis for obesity drug candidates
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