Acid-PEG12-CHO , CAS No.A1446931

CAS: A1446931 Cat. No.: A1446931 Fórmula: C₂₇H₅₂O₁₅ Peso molecular: 616.69

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Visão geral

Acid-PEG12-CHO is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs.

Specifications

Condições de armazenamento de armazenamento

Store at -20°C

Enviado em

Ice chest + Ice pads

Este produto requer transporte de cadeia fria. Serviços terrestres e outros serviços econômicos não estão disponíveis.

Nomes e identificadores

Peso molecular

616.69

Application Protocols

No tested application protocols, assays, or methods are provided in the Product Data for this item. For research use, users typically develop project-specific protocols for amide coupling, oxime/hydrazone ligation, or reductive amination. Refer to the literature and your institutional SOPs for method development, and consult the CoA/Spec Sheet for any item-specific handling recommendations.

Biological Roles

This product is a synthetic heterobifunctional PEG linker intended for research use; it is not a natural metabolite. The following points describe general, literature-based roles of PEG linkers in biochemical contexts (not product-specific and not clinical claims):

• PEG as an inert spacer: Poly(ethylene glycol) chains are widely used to increase aqueous solubility, reduce non-specific interactions, and modulate hydrodynamic size of conjugates. A PEG12 segment provides a flexible, hydrophilic spacer separating functional entities by several nanometers.
• Presentation of orthogonal reactivity: The aldehyde end can selectively react with nucleophiles introduced on biomolecules (e.g., hydrazides on proteins, hydroxylamine-derivatized probes, or aldehydes generated by periodate oxidation of glycans). The carboxyl end forms amide bonds to lysine-like amines after activation.
• Biophysical effects: PEGylation can reduce protein aggregation and surface fouling in vitro, and can space recognition elements away from surfaces to improve binding in biosensors. The magnitude of these effects depends on chain length, grafting density, and conjugation site.
• Aqueous compatibility: Many aldehyde ligations are water-compatible at mildly acidic to neutral pH, facilitating work with sensitive biomolecules under gentle conditions.

Note: No in vivo/therapeutic roles are implied. Performance in any biological assay is system-dependent; verify compatibility experimentally for your application.

Buffer Applications

While Acid-PEG12-CHO is not itself a buffering agent, buffers are integral to its use in bioconjugation. The following guidance is general/literature-based (not product-specific):

• Oxime/hydrazone ligation buffers:
  • Acetate buffer, pH 4.5–5.5, 50–200 mM; optional 10–30% acetonitrile or DMF for solubilization. Aniline (10–100 mM) can catalyze oxime/hydrazone formation.
  • Citrate–phosphate buffers (pH 4–6) provide broader buffering but may coordinate metals if present.
• Reductive amination:
  • Sodium acetate or phosphate buffer, pH ~5.5–6.5, with sodium cyanoborohydride or alternative mild hydride donors. Keep primary amine in slight excess.
• Amide coupling at the carboxyl end:
  • MES buffer (pH 5.0–6.5) with EDC/sulfo-NHS to minimize O-acylisourea hydrolysis; reaction with amines proceeds near neutral pH after NHS ester formation.
  • Phosphate-buffered saline (PBS) at pH 7.2–7.6 is common for the amine capture step; avoid primary amines (e.g., Tris) during NHS activation as they can quench the active ester.
• Compatibility notes:
  • Avoid high concentrations of competing nucleophiles (primary amines, hydrazides, hydroxylamine) unless they are intended reactants.
  • Control ionic strength to balance solubility and reaction rate; PEG linkers tolerate salts well.

These are general recommendations; optimize buffer composition for your specific substrate and analytical needs.

Green Alternatives

Greener choices relate primarily to solvent systems and coupling reagents (general guidance; not item-specific).

Solvent selection upgrades

• Prefer water or aqueous buffers for oxime/hydrazone ligations; these reactions are compatible with high water content and avoid dipolar aprotic solvents.
• If organic cosolvent is needed, consider ethanol or 2-propanol instead of DMF/NMP where feasible. For less water-tolerant steps, acetonitrile is often preferable to DMF due to lower toxicity and easier removal.

Coupling chemistry considerations

• Use water-soluble carbodiimide EDC with sulfo-NHS in buffered aqueous media to reduce reliance on DMF/DMSO.
• Explore enzyme-mediated couplings (e.g., microbial transglutaminase for amide formation) when substrates allow, minimizing hazardous reagents.

Comparison snapshot (literature/general)

• DMF vs Water-based EDC chemistry: Water reduces worker exposure and waste persistence; may require pH control and buffering capacity.
• NMP vs ACN/Ethanol cosolvent: ACN/ethanol offer lower reproductive toxicity and simpler solvent recovery.
• Sodium cyanoborohydride vs alternatives: Pyridine–borane or 2-picoline borane can be milder and offer improved handling; nonetheless, all hydride donors require appropriate EHS controls.

Process tips

• Maximize solids concentration to cut solvent volumes; use lyophilization from water/tert-butanol blends for isolation.
• Implement in-line desalting (size-exclusion or ultrafiltration) to minimize solvent-intensive chromatographic steps.
• Always assess EHS tradeoffs alongside yield, purity, and product stability.

Pharmaceutical Uses

No therapeutic or clinical claims are made for this product. The following describes general, non-clinical roles of PEG linkers in pharmaceutical research and manufacturing contexts (literature/general; not product-specific):

• Process development tools: Heterobifunctional PEG linkers like Acid-PEG12-CHO are used in conjugation method development to connect amine-bearing entities to aldehyde-reactive partners, aiding structure–activity relationship exploration for bioconjugates.
• Excipient-like behavior: The PEG12 spacer imparts hydrophilicity and can enhance solubility of conjugates in formulation screening. PEG chains can reduce non-specific adsorption during analytical handling.
• Surface and device modification: Aldehyde-terminated PEGs enable functionalization of diagnostic surfaces, affinity resins, and biosensor chips, improving anti-fouling and spacing of capture ligands.
• Analytical standards and linkers: Serve as spacers in reference materials or as handles for immobilization in assay development.

Regulatory and quality notes

• Pharmacopeial status: Not specified for this item; typically, custom PEG linkers are not monographed. For GMP use, define specifications (identity, purity, residuals, bioburden/endotoxin where applicable) and qualify suppliers.
• Extractables/leachables: When used with device materials, assess under intended conditions.
• Documentation: For any regulated work, rely on lot-specific CoA/Spec Sheet and develop validated analytical methods for end-group integrity and MW distribution.

Physical Properties

Item-specific values

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular Weight: Not specified for this item; refer to CoA/Spec Sheet.

Literature/general expectations for PEG12 aldehyde/carboxyl linkers (informational; not specifications)

• Physical state: PEGs around 12 EO units are commonly low-melting waxy solids or viscous oils, depending on exact end-groups and distribution.
• Solubility: Typically highly soluble in water and polar organic solvents (e.g., methanol, ethanol, acetonitrile, DMF, DMSO). Solubility in nonpolar solvents (e.g., hexanes, toluene) is limited due to the polar polyether backbone and ionic/ionizable acid end-group.
• LogP: Often strongly negative/apparent hydrophilicity due to multiple ether oxygens (exact value depends on end-groups; not specified for this item).
• pKa: Carboxylic acid pKa typically ~4–5 (literature, depends on microenvironment). Aldehyde is non-basic and undergoes hydration in water.
• Refractive index, density, BP/MP: Not typically reported as sharp values for PEG oligomers; values depend on distribution and are not specified for this item.

Practical notes

• Aldehyde functionality can exist partly as geminal diol in aqueous media, influencing reactivity in imine/oxime/hydrazone formation.
• Viscosity increases with chain length and concentration; warming gently (ambient to ~30 °C) often facilitates dissolution in water or polar organics. Avoid overheating to prevent degradation of end-groups.

Quality and Grades

Item-specific quality information

• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.

Guidance on grades for PEG-based linkers (general)

• Research grade: Suitable for most discovery chemistry and bioconjugation method development. Typical controls include low residual solvents/metals and confirmation of end-group integrity by NMR/MS (actual limits are product-specific; see CoA).
• High-purity/bioconjugation grade: Often emphasizes end-group fidelity, narrow polydispersity, and low UV/background absorbance for analytical workflows.
• Stabilizers: PEG aldehydes are usually supplied neat without stabilizers; some vendors protect aldehydes as acetals for stability. This item does not specify stabilizers—refer to CoA/Spec Sheet.

What to verify before critical use

• End-group integrity: Confirm presence of both –CO2H and –CHO (e.g., 1H NMR aldehydic signal, derivatization tests, HRMS).
• Polydispersity: PEG oligomers are distributions; verify average MW and dispersity if chain length is critical.
• Residual water/solvent content and UV background: Important for sensitive bioconjugations or analytical detection—values are not specified here; consult CoA.

Documentation

• For batch-specific specifications, acceptance criteria, and analytical data (NMR, MS, HPLC/SEC), refer to the CoA/Spec Sheet.

Reaction and Applications

Application domain (general for Acid-PEGn-CHO linkers)

• Heterobifunctional spacer enabling orthogonal conjugations between carboxylate-reactive partners (amide formation) and aldehyde-reactive partners (imine, hydrazone, oxime, or reductive amination), facilitating bioconjugation, surface modification, and polymer/materials functionalization.

Representative transformations (literature/general)

• Amide formation at the acid terminus:
  • Carbodiimide couplings (EDC or DIC) with NHS or sulfo-NHS to form active esters, then reaction with primary amines at pH ~7.0–8.5.
  • Water-compatible coupling using EDC/sulfo-NHS in MES or phosphate buffers, with minimal organic cosolvent.
• Aldehyde end-group chemistry:
  • Oxime ligation with hydroxylamines, typically pH 4.5–5.5, accelerated by aniline catalysts; forms hydrolytically robust oximes.
  • Hydrazone formation with hydrazides; stabilizable via aniline catalysis or reductive amination (NaBH3CN) to secondary amines.
  • Direct reductive amination with primary amines (pH ~5.5–6.5), using cyanoborohydride or pyridine–borane.

Use cases

• Site-selective conjugation to biomolecules (e.g., aldehyde end to oxidized glycan chains or N-terminal serine/threonine after periodate treatment; acid end to lysine amines via activated ester).
• Surface and nanoparticle modification: Coupling to amine-functional substrates while presenting an aldehyde handle for subsequent capture of hydrazide/oxime probes.

Practical tips

• Keep aldehyde exposure to strong base minimal to avoid side reactions.
• Verify end-group conversion by 1H NMR (disappearance of aldehydic proton) or LC-MS after ligation.
• For aqueous work, use degassed buffers to limit oxidative side reactions.

Reaction Conditions

General, literature-based guidance (not specifications for this item; optimize per system)

Amide coupling at the acid terminus

• Solvent: DMF, DMSO, NMP, or water/DMF mixtures; for aqueous EDC/sulfo-NHS activation, use MES (pH 5.0–6.5).
• Reagents: EDC (1.1–1.5 eq), NHS or sulfo-NHS (1.1–2.0 eq), base (DIPEA, 2–4 eq) for organic media; buffer controls pH in water.
• Temperature/time: 20–25 °C, 1–16 h. Monitor by LC-MS. Avoid strong bases that may degrade aldehyde.

Oxime/hydrazone formation at the aldehyde terminus

• Solvent/buffer: 50–200 mM acetate, pH 4.5–5.5, optionally 10–30% ACN or DMF; aniline (10–100 mM) as catalyst.
• Stoichiometry: Slight excess of nucleophile (1.2–2.0 eq). Reaction times 0.5–6 h at 20–25 °C.
• Notes: Oximes are typically more hydrolytically stable than hydrazones; for permanence, reduce to secondary amines (NaBH3CN or 2-picoline borane) at pH ~5.5–6.5.

Reductive amination

• Buffer: Sodium acetate or phosphate, pH 5.5–6.5.
• Reductant: NaBH3CN (1.5–3 eq) or pyridine–borane under inert atmosphere.
• Conditions: 20–25 °C, 2–16 h. Remove excess reductant carefully; quench with acid and purify.

Workup and purification

• PEGs often purify well by preparative reversed-phase HPLC (water/ACN with 0.1% formic acid) or by dialysis/SEC for macromolecular conjugates.
• Drying: Lyophilization preserves labile aldehyde-derived linkages; avoid high heat/vacuum that may promote end-group loss.

Expected outcomes

• Yields are substrate-dependent; PEGylation steps commonly provide moderate to high conversions with proper pH and stoichiometry control.

Safety and Handling

Item-specific hazard data

• GHS Classification: Not specified for this item; refer to SDS.
• Signal Word: Not specified for this item; refer to SDS.
• Hazard (H-) Statements: Not specified for this item; refer to SDS.
• Pictograms: Not specified for this item; refer to SDS.

General safety considerations for aldehyde-/acid-terminated PEG linkers (informational; defer to SDS)

• Hazard profile: PEG backbones are generally of low acute toxicity, while aldehydes are electrophilic and can be irritating to skin, eyes, and respiratory tract. The carboxylic acid may be mildly irritating.
• PPE: Wear lab coat, safety glasses or face shield, and appropriate chemical-resistant gloves (e.g., nitrile). Use in a fume hood to minimize exposure to vapors/aerosols during weighing and dissolution.
• Handling: Avoid inhalation of dust/aerosols. Prevent contact with oxidizing agents and strong bases/acids that can degrade aldehyde or promote side reactions. Minimize exposure of aldehyde to prolonged aqueous basic conditions to limit Cannizzaro-type processes.
• First aid (overview; follow institutional protocols):
  • Skin/eye contact: Rinse with water for at least 15 minutes; remove contaminated clothing. Seek medical attention if irritation persists.
  • Inhalation: Move to fresh air; seek medical advice if symptoms occur.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Waste: Collect aqueous and organic solutions in halogen-free organic or aqueous waste streams per institutional guidelines. Aldehyde-containing wastes may require specific handling.
• Always consult the SDS for authoritative safety and regulatory information. Research use only.

Solvent Selection

Solubility and polarity profile (general for PEG12 linkers)

• Strongly hydrophilic due to multiple ether oxygens and an ionizable carboxylic acid. Typically:
  • Miscible/very soluble: Water (especially as carboxylate), methanol, ethanol, isopropanol, acetonitrile, acetone, DMF, DMSO.
  • Limited solubility: Ethers like MTBE, CPME; chlorinated solvents; aromatics (toluene) unless aided by cosolvents.

Choosing solvents by task

• Amide coupling (–CO2H end): DMF, DMSO, NMP, or water/DMF mixtures are commonly used. For aqueous coupling (carbodiimide chemistry), MES or phosphate buffers with limited organic cosolvent are typical.
• Aldehyde ligations: Oxime/hydrazone formation proceeds in aqueous acetate or phosphate buffers (pH ~4.5–6.0), optionally with 10–30% ACN or DMF to assist solubilization. Reductive amination often uses aqueous buffer with MeOH/EtOH or DMF as cosolvent.
• Purification: Water-rich mobile phases (HPLC) or lyophilization from water/tert-butanol are common for PEGs.

Small comparison (literature/general)

• Water vs DMF: Water is greener and compatible with oxime/hydrazone chemistry; DMF enhances solubility and coupling efficiency for amide formation but has higher EHS burden.
• ACN vs DMSO: ACN aids desalting and HPLC compatibility; DMSO maximizes solubility but can complicate downstream removal.

Tips

• Adjust pH to deprotonate –CO2H for dissolution in water (forming carboxylate). For aldehyde reactions, maintain target pH to balance solubility and reactivity.

Storage and Reconstitution

Item-specific storage and shipping

• Storage Conditions: Store at -20°C (from Product Data).
• Shipped In: Ice chest + Ice pads (from Product Data).
• Research Use Note: For research use only.

General handling guidance (informational; not product-specific specifications)

• Protect the aldehyde from prolonged exposure to basic aqueous conditions and from strong oxidants/reductants to preserve end-group integrity.
• For short-term use, store tightly capped under dry conditions; consider inert atmosphere to limit oxidation/hydration. For long-term storage, -20°C as provided is appropriate.

Reconstitution (general suggestions)

• Solvents: Water, buffer, DMF, or DMSO are commonly suitable for PEG12 linkers. Begin with a small test aliquot to confirm solubility and stability in the chosen medium.
• Concentration: Prepare concentrated stocks (e.g., 10–100 mM) in water or DMF/DMSO depending on application; filter-sterilize if required for biochemical work.
• Aliquoting: To minimize freeze–thaw cycles, prepare single-use aliquots and store at -20°C. Allow vials to warm to room temperature in a desiccator before opening to prevent moisture condensation.

Note: For definitive storage limits, stability, and any preservative/stabilizer information, refer to the lot-specific CoA/Spec Sheet and SDS.

Structure and Identity

Item-specific identifiers (from Product Data)

• SKU: A1446931
• Product Name: Acid-PEG12-CHO
• CAS: A1446931 (catalog placeholder)
• Molecular Formula: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular Weight: Not specified for this item; refer to CoA/Spec Sheet.
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet.

General structural description (literature/general)

• Functional class: Heterobifunctional polyethylene glycol (PEG) linker bearing a terminal carboxylic acid (–CO2H) at one end and an aldehyde (–CHO) at the other.
• PEG length: “PEG12” denotes a chain of 12 ethylene glycol repeat units, i.e., –(O–CH2–CH2)12–, providing a hydrophilic, flexible spacer of low polydispersity (exact distribution is product-specific; see CoA where provided).
• Structural features: Linear, aliphatic polyether backbone with two orthogonal reactive termini: a Brønsted-acidic carboxyl group and an electrophilic aldehyde capable of imine/hydrazone/oxime formation.
• 2D description in words: One terminus is a carboxylic acid connected to a linear sequence of twelve –CH2–CH2–O– units; the chain terminates in a methylene-aldehyde group (–CH2–CHO). No stereocenters are present; the backbone is conformationally flexible.

Notes

• Exact counter-ions (if any), end-group protection, and polydispersity are not specified for this item; refer to CoA/Spec Sheet for definitive identity data.

Synthetic Utility

Functional group orthogonality

• Carboxylic acid terminus: Readily transformed into amides, esters, acyl azides, or activated esters (e.g., NHS esters). Compatible with carbodiimide (EDC/DIC) and uronium (HATU/TBTU) coupling regimes.
• Aldehyde terminus: Engages in imine formation with primary amines; hydrazone formation with hydrazides; oxime ligation with hydroxylamines; reductive amination to secondary amines. Protectable as acetals (e.g., dimethyl acetal) for multi-step syntheses.

Spacer role in retrosynthesis

• Acid-PEG12-CHO acts as a hydrophilic, length-defined spacer to bridge two motifs while minimizing electronic communication. The PEG backbone can improve solubility of otherwise lipophilic intermediates and intermediates can be purified by water-rich methods.

Representative synthetic maneuvers (literature/general)

• Sequential orthogonal couplings: Protect the aldehyde as an acetal, acylate the acid to the desired amide/ester, then deprotect to reveal the aldehyde for final ligation.
• Convergent assembly: Pre-form an NHS ester at the acid end, isolate or use in situ, then perform aldehyde ligation to a hydrazide-tagged partner.
• Click alternatives: If aldehyde chemistry is undesirable, convert the acid to an azide/alkyne-bearing handle and use CuAAC or strain-promoted cycloadditions at the other end.

Practical tips

• Monitor reactions by LC-MS; PEGs show characteristic mass spacing (+44 Da per EO unit). Suppress adducts (Na+/K+) by adding ammonium salts or using metal-free glassware.
• For scale-up, manage viscosity by temperature control and solvent choice; semi-batch addition can improve mixing.

Target Specificity

Not applicable to this chemical reagent. Acid-PEG12-CHO is a small-molecule linker and does not have biological target specificity, antigen reactivity, clone, or isotype. No target-related data are provided in the Product Data.

Perguntas frequentes

How should this product be stored?

Store at ?20 °C. Freezer storage is required to maintain the specified shelf life.

How is this product shipped?

This product ships in an insulated container with ice pads. Unpack on arrival and transfer it to the storage condition stated above.

What are the CAS number, molecular formula and molecular weight?

The CAS Number is A1446931, the molecular formula is C27H52O15, and the molecular weight is 616.69 g/mol.

What documentation is provided?

Available product documentation, including Certificates of Analysis (COA), Safety Data Sheets (SDS), and specification sheets, is shown in the product document area. Document availability and access follow the current site policy.