Amino-PEG11-acid , CAS No.1616426-12-0

CAS: 1616426-12-0 Cat. No.: A1445158 Formula: C₂₅H₅₁NO₁₃ Peso molecolare: 573.67

Storage

Protected from light,Room temperature,Desiccated

Shipped In

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Panoramica

Amino-PEG11-acid is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs.

Specifiche

Condizioni di conservazione di stoccaggio

Protected from light,Room temperature,Desiccated

Spedito in

Normal

Nomi e identificatori

Peso molecolare

573.67

Application Protocols

Item-specific validated protocols are not provided. The following generalized procedures illustrate common uses (literature/general guidance):

1. EDC/NHS activation of the carboxylate and coupling to an amine-bearing substrate

• Dissolve Amino-PEG11-acid at 10–50 mM in 50 mM MES, pH 5.5 (add 10–20% DMF if needed).
• Add NHS (5–10 equiv) and EDC·HCl (5–10 equiv); stir 15–30 min at RT to generate the NHS ester in situ.
• Exchange buffer to pH 7.5–8.3 (e.g., PBS) and add the amine-bearing partner (1.2–2.0 equiv). React 1–2 h at RT.
• Quench with 50 mM ethanolamine, 15 min. Purify by RP-HPLC or dialysis, as appropriate.

2. Coupling the amine terminus to an NHS ester-functionalized dye/small molecule

• Prepare 10–50 mM linker solution in 50 mM bicarbonate buffer, pH 8.3 (≤20% DMF for solubility).
• Add NHS-activated partner (1.1–1.5 equiv) and incubate 30–90 min at RT.
• Quench unreacted NHS ester with Tris; purify by RP-HPLC.

3. Surface passivation of carboxylated nanoparticles (schematic)

• Disperse particles in MES, pH 5.5; add EDC/NHS (5–10 equiv per surface COOH) and Amino-PEG11-acid (excess).
• React 30–60 min, RT; wash by centrifugation and resuspension. Characterize by DLS and zeta potential.

Adjust concentrations and stoichiometries to substrate loading and desired grafting density.

Biological Roles

Amino-PEG11-acid is a synthetic, non-natural linker; it does not have endogenous biological roles. However, PEG spacers of defined length are widely used in biochemical systems to modulate biophysical properties (literature/general):

• Hydrophilicity and stealth: PEG chains reduce protein adsorption and can diminish nonspecific interactions in complex matrices, improving signal-to-noise in assays and on sensor surfaces.
• Spatial separation: The ≈11-unit PEG segment introduces a flexible, ~3–4 nm hydration shell/contour length (order-of-magnitude, literature), distancing conjugated cargos from surfaces or biomolecular scaffolds to mitigate steric hindrance.
• Solubility enhancement: Attachment of PEG linkers to hydrophobic ligands or dyes improves aqueous handling and reduces aggregation.
• Tunable reactivity: The amine and acid termini enable orthogonal conjugation to biomolecules bearing carboxylates (via EDC/NHS) or amines (via NHS esters/activated carbonyls), facilitating site-selective modifications when appropriate targeting strategies are used.

No medical/clinical claims are made. Use is limited to research and laboratory applications, including preparation of PEGylated probes, enzyme substrates, affinity ligands, and surface passivation layers for in vitro studies.

Buffer Applications

This product is not a buffering agent. However, buffer selection is critical for its use in aqueous conjugation reactions (literature/general):

• EDC/NHS activation of the carboxylate terminus:
  • Use acidic to mildly acidic buffers lacking primary amines: MES (pH 4.7–6.0) or acetate (pH 4.5–5.5). Avoid Tris, glycine, or other nucleophilic buffers.
  • Typical recipe (example): 50 mM MES, 150 mM NaCl, pH 5.5; dissolve linker, add NHS (5–10 equiv) and EDC (5–10 equiv), activate 10–30 min at RT.
• Coupling NHS-activated linker to amines on biomolecules:
  • Shift to neutral to slightly basic buffers: PBS, HEPES, or sodium bicarbonate/carbonate (pH 7.5–8.5) to promote amine nucleophilicity.
  • Keep organic cosolvent ≤20% v/v (DMF/ACN) for protein compatibility.
• Amine-terminus reactions (with NHS esters or acyl halides):
  • Perform in phosphate, HEPES, or bicarbonate buffers at pH 7.5–9.0 (for NHS esters) or in anhydrous organic solvent with base (for acyl halides).

Practical guidance:

• Remove competing nucleophiles (e.g., Tris, azide) during coupling.
• Control ionic strength to balance solubility and protein stability.
• For small-molecule couplings, organic media (DMF/ACN) with organic base may be preferred over aqueous buffers.

Green Alternatives

While Amino-PEG11-acid is itself a benign, non-volatile, and often water-compatible linker, the coupling chemistries and solvents chosen can dominate the environmental footprint. Greener strategies (literature/general):

• Solvent choices:
  • Prefer water or water/ethanol mixtures when feasible for EDC/NHS couplings.
  • Replace DMF/NMP with acetonitrile or 2-MeTHF when compatible; consider propylene carbonate or Cyrene as emerging greener polar aprotic media.
• Coupling reagents:
  • Use water-soluble carbodiimides (EDC) in buffered aqueous media rather than HATU/HBTU (which are more hazardous and generate persistent waste).
  • DMTMM (4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride) enables amide formation in water or MeOH with minimal byproducts.
• Process intensification:
  • Run at higher concentrations to reduce solvent volume; use in situ activation and one-pot protocols to minimize workups.
  • Employ solid-supported scavengers to simplify purification and reduce solvent usage.

Comparison (general):

• EDC/NHS in MES buffer vs. HATU in DMF
  • Safety/greenness: EDC/NHS aqueous system is typically safer and greener.
  • Performance: HATU often gives higher rates in challenging couplings but with more hazardous profile.
• Water/EtOH vs. DMF
  • Water/EtOH is preferable where substrates tolerate; DMF offers broader solubility but carries reproductive toxicity concerns.

Conclusion: Favor aqueous or biofriendly solvents and carbodiimide/DMTMM activations where possible to leverage the inherent water compatibility of the PEG11 linker.

Pharmaceutical Uses

No therapeutic claims are made. For research and process development contexts (literature/general):

• Role as a linker/excipient:
  • Serves as a hydrophilic spacer in conjugates (e.g., attaching ligands, dyes, or polymers) to improve solubility and reduce aggregation of research candidates.
  • Provides steric shielding in prototype delivery systems and surface passivation in device coatings.
• Formulation considerations:
  • PEG linkers can enhance aqueous compatibility of hydrophobic actives in preformulation studies.
  • The amine and acid termini allow incorporation into pro-moieties or polymer backbones for exploratory structure–property optimization.
• Regulatory status:
  • No pharmacopeial monograph is implied for this specific item. PEGs as a class may appear in pharmacopeias, but oligomer-specific entries and bifunctional derivatives are typically not monographed. Confirm regulatory acceptability separately.
• Analytical development:
  • Characterize conjugates by LC–MS, SEC, and capillary electrophoresis; assess residual coupling reagents and byproducts.
  • Stability-indicating methods should monitor hydrolysis of amide/ester bonds and potential oxidative degradation (ethers are generally stable, but impurities may oxidize under harsh conditions).

All uses are restricted to research/laboratory settings.

Physical Properties

Item-specific physicochemical constants are not provided in the product data. The following are general characteristics of heterobifunctional PEG linkers bearing 10–12 oxyethylene units (literature/general guidance):

• Appearance: Not specified for this item; refer to CoA/Spec Sheet. (Similar PEG oligomers are often white to off-white solids or waxy.)
• Molecular weight and formula: Not specified for this item; refer to CoA/Spec Sheet.
• Melting point, boiling point, density, refractive index: Not specified for this item; refer to CoA/Spec Sheet.
• Hygroscopicity: PEG oligomers are typically hygroscopic; store desiccated (product data indicates desiccation).
• Solubility (literature/general):
  • High solubility in water and polar protic solvents (e.g., methanol, ethanol).
  • Good solubility in polar aprotic solvents (e.g., DMF, DMSO, acetonitrile).
  • Limited solubility in nonpolar solvents (e.g., hexanes, toluene) due to PEG polarity.
• pKa (functional groups, literature/general):
  • Carboxylic acid: pKa typically ~4–5 for aliphatic acids; ionized above neutral pH.
  • Terminal primary amine: conjugate acid pKa typically ~9–10; protonated under mildly acidic conditions.
• LogP: PEGylation greatly reduces logP; oligomers of this length are strongly hydrophilic (literature).
• UV/Vis: PEG backbones exhibit minimal absorbance >220–230 nm; chromophores are absent. Specific UV cutoff is not specified for this item.

For quantitative specifications (water content, metal limits, exact solubilities), consult the CoA/Spec Sheet.

Quality and Grades

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

Context for PEG linker quality (general):

• Purity descriptors you may encounter for similar products include:
  • Research grade (>95% by HPLC or NMR, typical for synthetic linkers).
  • Low-water/anhydrous grades for moisture-sensitive coupling.
  • Monodisperse (discrete) vs. polydisperse PEG: Monodisperse products display a single defined n; polydisperse show a distribution (Ð). This listing does not specify dispersity; consult CoA.
• Common QC/acceptance tests (general):
  • Identity by 1H/13C NMR and/or HRMS.
  • Purity by HPLC/UPLC or GPC (for dispersity assessment).
  • Residual solvents and water (Karl Fischer).
  • Functional assay (e.g., titration of amine/acid functionality) to confirm bifunctionality.
• Stabilizers/Additives: Typically none for PEG linkers; if stabilizers or salts (e.g., TFA) are present, they are stated on the CoA. Not specified for this item.
• UV specifications for chromatography applications (HPLC grade) are relevant for solvents; for PEG linkers, low baseline absorbance is common but no UV cutoff is specified.

Recommendation: Verify the required parameters for your application (purity, water content, dispersity, residual metals/solvents) in the CoA/Spec Sheet for this specific lot.

Reaction and Applications

Amino-PEG11-acid serves as a versatile, hydrophilic, heterobifunctional spacer for building amide/urea/carbamate linkages between otherwise incompatible partners. Representative uses (literature/general):

• Bioconjugation and surface modification:
  • Convert the carboxylate terminus to an NHS ester (EDC/NHS or DIC/NHS), then couple to primary amines on peptides, proteins (lysines), or amine-functional surfaces.
  • Use the amine terminus to react with activated esters (NHS-esters), acyl chlorides/anhydrides, or isocyanates to form amides or ureas with small molecules, dyes, or polymers.
  • Grafting to nanoparticles (Au, SiO2, Fe3O4) and oxides via prior functionalization (e.g., EDC-mediated attachment to carboxyl-terminated SAMs or silanes bearing carboxyls).
• Linker engineering:
  • Introduce defined hydrophilic spacing (≈ 11 EG units) to reduce steric hindrance, improve aqueous solubility, and decrease nonspecific binding.
  • Facilitate “click-ready” handles by capping one end (e.g., amide formation) and transforming the other into azide/alkyne (via standard amine/acid conversions) for CuAAC/SPIEDAC workflows.
• Polymer and material synthesis:
  • Chain extension with diisocyanates or diacids to build segmented polyurethanes/polyamides with PEG soft segments.
  • Immobilization of catalysts/organics on solid supports to improve processability and recovery.

Practical considerations:

• Sequence control: Activate and couple one terminus at a time to avoid self-condensation; protect or protonate the off-target end.
• Aqueous compatibility: PEG backbone permits water-enabled couplings (e.g., EDC/NHS in MES), useful for biomolecule-friendly conditions.
• Purification: Product mixtures are often water-soluble; reverse-phase chromatography or dialysis (for macromolecules) is effective.

Reaction Conditions

Representative, literature-based conditions for each terminus (general guidance; optimize per substrate):

• Carboxylate terminus → amide (EDC/NHS, aqueous):
  • Dissolve linker in 50 mM MES buffer, pH 5.5 (±10–20% DMF if needed). Add NHS (5–10 equiv) and EDC·HCl (5–10 equiv). Stir 10–30 min at 20–25°C to form the NHS ester (monitor by LC–MS).
  • Add amine-bearing partner in PBS/HEPES, adjust pH 7.5–8.3, react 1–2 h at RT (or 4–16 h at 4°C for proteins). Quench residual NHS ester with Tris or ethanolamine.
  • Typical yields for small-molecule couplings: 70–90% (literature range), dependent on sterics and solubility.
• Carboxylate terminus → amide (HATU, anhydrous):
  • Anhydrous DMF or MeCN, 0.05–0.2 M; HATU (1.1–1.5 equiv), DIPEA (2–3 equiv), 0–25°C, 0.5–3 h. Work up by aqueous quench and extract or precipitate.
• Amine terminus → amide (with NHS ester partner):
  • Buffer pH 7.5–8.5 (borate, bicarbonate, or HEPES), 20–25°C, 0.5–2 h. Organic cosolvent ≤20% for biomolecules.
• Amine terminus → urea (with isocyanate):
  • Dry acetonitrile or DMF, 0.05–0.2 M, 0–25°C, 1–4 h; add base (e.g., DIPEA, 1–2 equiv) if needed. Moisture exclusion required.

Operational tips:

• Keep moisture low during activation; PEGs are hygroscopic—work quickly from desiccator to reaction.
• If both ends are reactive under conditions, protect or temporarily protonate the non-target end (e.g., run EDC activation at pH ~5.5 to suppress amine nucleophilicity).
• For workup, exploit PEG solubility: partition into water, then remove small-molecule impurities by dialysis (bioconjugates) or use RP-HPLC for discrete products.

Safety and Handling

GHS classification, pictograms, and hazard statements are not provided in the product data. Handle according to good laboratory practice and refer to the SDS for authoritative guidance.

• GHS/Signal word/H-statements: Not specified for this item; refer to SDS.
• Likely hazards (general for PEG linkers): Low volatility solids with low acute toxicity; may cause skin/eye/respiratory irritation. Avoid dust generation and inhalation.
• Storage (item-specific):
  • Protect from light.
  • Store at room temperature.
  • Keep desiccated (hygroscopic). Close container tightly and use desiccant packs.
• Incompatibilities (general): Strong oxidizers; strong acids/bases may promote hydrolysis of activated derivatives (e.g., NHS esters formed in situ). Avoid moisture during coupling reagent handling.
• PPE: Lab coat, safety glasses, and appropriate chemically resistant gloves (e.g., nitrile). Use in a fume hood when handling coupling reagents (EDC/HATU/HBTU, etc.).
• First aid (general):
  • Skin/eye contact: Rinse with water for several minutes; remove contaminated clothing; seek medical attention if irritation persists.
  • Inhalation: Move to fresh air; seek medical attention if symptoms occur.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Waste: Dispose of PEG-containing and coupling-reagent wastes per institutional guidelines and local regulations. Segregate amide-coupling byproducts (e.g., ureas from carbodiimides) as hazardous organic waste.

Always consult the SDS for this specific item before use.

Solvent Selection

Amino-PEG11-acid is highly polar and generally dissolves well in aqueous and polar organic media (literature/general). Solvent choice should reflect both dissolution and intended coupling chemistry.

• Polarity/miscibility (general):
  • Water: Typically soluble at moderate to high concentrations; adjust pH to modulate ionization (COOH/–NH2).
  • Polar aprotic: DMSO, DMF, and acetonitrile usually dissolve PEG11 linkers readily; excellent for amide couplings with base.
  • Alcohols: Methanol/ethanol often suitable for formulation or intermediate handling; less favored for carbodiimide-mediated activations.
  • Nonpolar: Poorly soluble in hydrocarbons and chlorinated solvents due to PEG polarity.
• Choosing a solvent by task:
  • EDC/NHS activation of the acid: MES buffer (pH 4.7–6.0) or mildly acidic aqueous media minimize amine protonation side reactions; DMF cosolvent can aid dissolution.
  • HATU/HBTU/DIC couplings: Anhydrous DMF, NMP, or acetonitrile with DIPEA/TEA base are common.
  • Protein/biomolecule conjugation: Buffered aqueous media (PBS, HEPES) with pre-formed NHS ester; limit organic cosolvent to <20% v/v to preserve biomolecule stability.
  • Stock solutions: Anhydrous DMSO or DMF at 10–100 mM for small-molecule conjugations; dilute into reaction buffer immediately before use.
• Practical tips:
  • Remove dissolved oxygen/moisture for moisture-sensitive activations; use freshly opened anhydrous solvents.
  • If both termini are reactive under chosen conditions, consider temporary protection or orthogonal sequencing.

Storage and Reconstitution

• Storage conditions (item-specific):

  • Protected from light.
  • Room temperature.
  • Desiccated.
  • Shipped: Normal conditions (ambient) per product data.

• Container handling:

  • Keep tightly closed with desiccant; minimize headspace humidity. Open only at ambient conditions with low RH if possible.
  • Reseal promptly after use; consider aliquoting upon first opening to limit moisture uptake.

• Reconstitution (general guidance):

  • Aqueous: Dissolve directly in deionized water or buffer appropriate to the reaction (e.g., MES pH ~5.5 for EDC activation; PBS/HEPES pH 7.5–8.5 for NHS-amine couplings).
  • Organic: Prepare concentrated stocks (e.g., 10–100 mM) in anhydrous DMSO, DMF, or acetonitrile for small-molecule couplings. Filter (0.22 µm) if needed.
  • For protein conjugations, avoid high DMSO content; keep organic cosolvent ≤10–20% v/v.

• Stability considerations (general):

  • The parent amine/acid linker is generally stable when dry and protected from light. Activated derivatives (e.g., NHS esters) are moisture-sensitive; prepare immediately before use and store on ice for short periods only.
  • Avoid repeated freeze–thaw of solutions; prepare single-use aliquots.

For exact shelf life, water content limits, and assay specifications, refer to the lot-specific CoA/Spec Sheet. Research use only.

Structure and Identity

Amino-PEG11-acid is a heterobifunctional poly(ethylene glycol) (PEG) linker bearing a terminal primary amine on one end and a terminal carboxylic acid on the other, separated by an oligomeric chain of eleven ethylene glycol repeat units. This architecture provides a hydrophilic, flexible spacer for conjugation chemistry.

• SKU: A1445158
• CAS: 1616426-12-0
• Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.

Structural features (general description):

• Linear PEG backbone comprising 11 –CH2–CH2–O– repeat units.
• One terminus: primary amine (–NH2), nucleophilic and readily acylated/carbamylated.
• Opposite terminus: carboxylic acid (–COOH), amenable to activation (e.g., NHS ester) and amide formation.
• Overall molecule is neutral but highly polar; PEG chain imparts water solubility and reduces nonspecific interactions.
• 2D depiction (verbal): H2N–(CH2–CH2–O)11–(CH2)x–COOH, where the PEG ether repeats form a flexible chain between two orthogonal functional handles. (Exact linker methylenes adjacent to termini vary by supplier; see CoA for definitive structure.)

Notes:

• PEG11 typically corresponds to an average or discrete oligomer length of eleven oxyethylene units (literature). Specific monodispersity vs. polydispersity is not specified for this item; refer to CoA/Spec Sheet.

Synthetic Utility

Functional group ensemble: primary amine (nucleophile/base) and carboxylic acid (electrophile after activation), tethered by an 11-unit PEG chain that imparts high polarity and flexibility.

Key transformations (literature/general):

• Amide formation at the acid terminus: activation by EDC/NHS, HATU, TBTU, DMTMM, CDI; coupling to amines on small molecules, peptides, resins, or surfaces.
• Urea/carbamate formation at the amine terminus: reaction with isocyanates/carbonates (e.g., DSC) to introduce activated carbonates for further reaction with nucleophiles (alcohols, amines).
• Selective protection strategies: Boc- or Fmoc-protection of the amine to enable first-stage coupling via the acid; methyl/benzyl ester protection of the acid to enable amine-first strategies. Subsequent deprotection under orthogonal conditions.
• Handle interconversions: conversion of the amine to azide (via diazo-transfer or via mesylation of a terminal hydroxyl if present in a derivative), or to alkyne (via amide to propargyl carboxamide), enabling click chemistry.
• Polymer conjugation: coupling to diacids/diisocyanates to create ABA or AB block motifs; installation of end-group diversity on PEGylated scaffolds.

Practical notes:

• Control pH and base equivalents to suppress intramolecular salt formation that can slow couplings.
• Employ stoichiometric excesses (1.2–1.5 equiv) of the activated partner to drive completion; monitor by LC–MS or HPLC.
• Purification options include reverse-phase chromatography and precipitation from ether/acetone for PEGylated products.

Target Specificity

Not applicable. This product is a chemical linker and does not possess inherent biological target specificity, antigen recognition, or clone/isotype properties. For specificity in bioconjugation, select targeting ligands (antibodies, peptides, small molecules) separately and couple them via the amine or acid terminus of this linker.