DSPE-PEG13-TFP ester , CAS No.D1447907

CAS: D1447907 Cat. No.: D1447907 Formule: C₇₇H₁₃₈F₄NO₂₄P Poids moléculaire: 1568.88

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Vue d’ensemble

DSPE-PEG13-TFP ester is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs.

Specifications

Conditions de stockage de stockage

Store at -20°C

Expédié en

Ice chest + Ice pads

Ce produit nécessite l'expédition en chaîne froide. Les services terrestres et autres services économiques ne sont pas disponibles.

Noms et identifiants

Poids moléculaire

1568.88

Application Protocols

The following general procedures illustrate typical laboratory uses. Adjust to your system and verify analytically.

• A. Amine conjugation in anhydrous DMF (general)

  1. Dry solvents and glassware. Dissolve DSPE-PEG13-TFP ester (e.g., 5–10 mg/mL) in anhydrous DMF under N2.
  2. Add primary amine ligand (1.5–2.0 eq) and DIPEA (1–2 eq). Stir at 25 °C for 4–12 h.
  3. Monitor by HPLC. Upon completion, quench residual active ester with 10 eq ethanolamine (optional), then precipitate into cold ether or perform dialysis/SEC.
  4. Dry under vacuum; store aliquots at −20 °C, desiccated.

• B. Aqueous-assisted peptide conjugation (general)

  1. Prepare HEPES buffer (50 mM, pH 8.0) free of amines; add 20% DMF.
  2. Dissolve peptide (amine-bearing) and DSPE-PEG13-TFP ester; keep total concentration 0.1–2 mM to manage viscosity/aggregation.
  3. React 1–4 h at 20 °C; monitor by LC–MS or HPLC. Purify by dialysis (MWCO appropriate for PEG13) or SEC.

• C. Liposome post-insertion (general)

  1. Warm preformed liposomes above DSPE Tm (~55 °C). Prepare DSPE-PEG–Ligand in warm buffer or 10–20% ethanol.
  2. Add to liposomes at desired mol% (e.g., 0.5–5 mol% of total lipid). Incubate 0.5–2 h with gentle mixing.
  3. Remove free conjugate by SEC (e.g., Sepharose CL-4B) or dialysis. Characterize by ligand assay and DLS.

Note: The above are literature-style examples, not item specifications. Optimize stoichiometry, temperature, and purification for your specific ligand and formulation.

Biological Roles

This product is intended for research use only; no clinical or therapeutic claims are implied.

• General biochemical context (literature)

  • DSPE is a saturated phospholipid that partitions strongly into the gel phase of bilayers; PEGylation imparts a hydrated corona that reduces protein adsorption and colloidal instability (the “stealth” effect in model systems).
  • When DSPE-PEG is incorporated into lipid assemblies, the PEG chain extends into the aqueous phase, modulating surface hydration, interparticle forces, and steric stabilization.
  • The TFP ester is not a biological moiety; it is a synthetic reactive handle that enables covalent attachment of amine-bearing biomolecules (peptides, proteins, glycans) to the PEG end, positioning ligands at membrane interfaces in vitro.

• Functional implications in models

  • Surface display: After amine conjugation, the resulting DSPE-PEG–Ligand can be used to study receptor–ligand interactions on supported bilayers, liposomes, or proteoliposomes.
  • Membrane biophysics: Inclusion of DSPE-PEG derivatives alters bending rigidity, lateral diffusion, and phase behavior, useful for probing crowding and steric effects in reconstituted systems.

• Metabolic fate

  • As a synthetic amphiphile, DSPE-PEG conjugates are generally not metabolized in the same pathways as native lipids in simplified in vitro systems; degradation can occur chemically (hydrolysis/oxidation) rather than enzymatically unless specific enzymes are present.

For organism-related behavior or toxicity, consult primary literature and perform system-specific validation.

Buffer Applications

This material is not a buffering reagent and is not typically used to set or maintain pH.

• Practical buffer-related notes (general)

  • For aqueous conjugation of the TFP ester to primary amines, use amine-free buffers such as HEPES or phosphate at pH 7.5–8.5. Avoid Tris or other primary amine buffers that will consume the TFP ester.
  • Maintain ionic strength compatible with your biomolecule; include 10–30% DMF/DMSO as needed for solubilization while completing the reaction promptly to minimize hydrolysis.

• Electrophoresis/cell culture

  • Not generally used as a buffer component in electrophoresis or cell culture; instead, it can be incorporated into vesicles or supported bilayers prepared in those buffers for biophysical studies.

Green Alternatives

While DSPE-PEG13-TFP ester often requires aprotic polar solvents for efficient conjugation, several greener choices or strategies can reduce environmental impact without compromising performance.

• Greener solvent strategies (general)

  • Replace dichloromethane with ethyl acetate or 2-MeTHF for film dissolution and workup when solubility permits.
  • Favor aqueous-buffered coupling (HEPES or phosphate, pH 7.5–8.5) with minimal DMF/DMSO co-solvent; TFP esters tolerate partial water better than NHS, but prompt processing is essential.
  • Use ethanol or isopropanol as co-solvents for liposome post-insertion below membrane-disruptive thresholds.

• Process intensification

  • Microscale or flow-assisted conjugations reduce solvent volumes and improve mass transfer.
  • Solvent recycling (DMF/DMSO) with appropriate purification and monitoring (water by KF) can cut waste.

• Comparative considerations (general)

| Aspect | Traditional option | Greener alternative | Trade-offs | |---|---|---|---| | Dissolution | CH2Cl2/CHCl3 | EtOAc/2-MeTHF | May need warming; slower dissolution | | Coupling medium | Anhydrous DMF | Buffered aq. + 10–20% DMF | Faster hydrolysis risk; monitor reaction | | Workup | Large-volume chlorinated washes | Precipitation/dialysis | Requires method optimization |

• Solid-form handling
  • Aliquot to minimize repeat thaw–dissolve cycles, reducing solvent use over time.

Note: Always verify product quality and coupling efficiency after process changes; greener substitutions may require condition re-optimization.

Pharmaceutical Uses

For research use only. The following describes typical formulation roles in laboratory and process-development contexts without implying suitability for clinical use.

• Excipient/formulation role (general)

  • Amphiphilic anchor: DSPE embeds in lipid bilayers or hydrophobic domains; PEG13 provides a hydrated spacer; the TFP ester allows installation of amine-bearing ligands to create functionalized excipient-like materials for investigative formulations (e.g., targeted liposomes in model systems).
  • Colloidal stabilization: PEG chains reduce aggregation and protein adsorption in vitro, aiding development of stable dispersions for research.

• Process development utilities

  • Post-insertion: DSPE-PEG–Ligand conjugates can be post-inserted into preformed vesicles at temperatures above DSPE’s phase transition to adjust surface composition late in the process flow.
  • Analytical comparability: Functionalized DSPE-PEG can serve as reference materials for assessing ligand density, binding, and stability on lipid-based particles.

• Regulatory/pharmacopeial status

  • No pharmacopeial designation is provided for this item. Any GMP or compendial compliance, if required, must be confirmed with item-specific documentation. Grade/purity: Not specified for this item; refer to CoA/Spec Sheet.

Users are responsible for determining suitability for their application and for obtaining any necessary regulatory clearances for non-research uses.

Physical Properties

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility (general/literature)
  • Organic: soluble in chloroform, dichloromethane, and polar aprotic solvents such as anhydrous DMF and DMSO; limited solubility in alcohols depending on temperature and water content.
  • Aqueous: forms micelles/aggregates; improved dispersion above PEG’s hydration temperature; reactive TFP ester hydrolyzes in water (see Safety/Handling).
• Aggregation/phase behavior (general)
  • Amphiphilic; can self-assemble into micelles or insert into lipid bilayers. Critical micelle concentration and phase transitions depend on PEG length, lipid composition, and temperature (literature values vary; consult specific formulation data).
• Thermal properties (general/literature)
  • DSPE acyl chains exhibit a gel–fluid transition typically around 54–55 °C for pure DSPE; PEGylation and solvent reduce cooperativity and apparent Tm.
• Partitioning (general)
  • Strongly lipophilic DSPE moiety (favors bilayer phase) with a hydrophilic PEG corona; overall behavior is amphiphilic rather than captured by a single logP.
• Refractive index, pKa, density, BP/MP: Not specified for this item; refer to CoA/Spec Sheet.

Note: Exact physicochemical constants for this specific conjugate are formulation- and lot-dependent due to PEG polydispersity; rely on the CoA for item-specific values.

Quality and Grades

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

• How quality is typically defined for lipid–PEG–TFP esters (general guidance)

  • Identity: Verified by 1H/13C NMR (organic solvent), MALDI-TOF/ESI-MS for average mass, and IR (ester, phosphate, PEG ether bands).
  • Purity: Assessed by RP-HPLC/UPLC (UV at ~215–230 nm and ~260–270 nm capturing aryl), SEC for high-MW impurities/aggregation, and TLC for organic-soluble intermediates.
  • Activated-ester content: Determined by titration with a model amine or by HPLC quantitation of released tetrafluorophenol after controlled hydrolysis.
  • Residual solvents, water, and inorganic ions: Typically assessed by GC, Karl Fischer, and ICP-OES (if applicable). Specific limits are item-dependent and must be confirmed on the CoA.

• Stabilization and handling implications

  • No stabilizer is normally required; activity is preserved by low temperature, desiccation, and exclusion of moisture.
  • Each thaw exposes the TFP ester to ambient humidity; aliquot under dry inert gas to maintain coupling efficiency.

• Documentation

  • For regulated workflows or analytical comparability, request the lot CoA including analytical methods, acceptance criteria, and release results. Item-specific specs (UV cutoff, metal limits, peroxide, water, etc.) are Not specified for this item; refer to CoA/Spec Sheet.

Reaction and Applications

• Principal reaction (general/literature)

  • The terminal 2,3,5,6-tetrafluorophenyl (TFP) ester undergoes nucleophilic acyl substitution with primary amines to form robust amide linkages. Electron-withdrawing fluorines enhance aryl oxide leaving-group ability, often affording higher conversions than NHS esters under partially aqueous conditions.

• Common applications in research workflows

  • Ligand conjugation: Install peptides, small-molecule amines, fluorophores, or polymers onto the PEG terminus, yielding DSPE-PEG-Ligand constructs for membrane display.
  • Liposome and LNP surface functionalization: Blend pre-conjugated DSPE-PEG–Ligand into lipid films or post-insert into preformed vesicles above DSPE Tm to present ligands on the particle corona.
  • Micelle/vesicle assembly: Create targeted or imaging-enabled nanostructures where DSPE anchors in the hydrophobic phase and PEG displays the cargo in the aqueous phase.
  • Surface passivation: Immobilize amine-bearing layers on solid supports to generate PEGylated, lipid-mimetic interfaces reducing nonspecific adsorption.

• Practical coupling guidance

  • Use anhydrous DMF/DMSO with 1.2–3.0 eq amine and 1–2 eq tertiary base (e.g., DIPEA); exclude water and perform under N2/Ar. For aqueous-compatible protocols, maintain pH 7.5–8.5 with minimal organic co-solvent and react promptly (hours) to outrun hydrolysis.
  • Monitor by HPLC or LC–MS via consumption of the TFP-ester peak or appearance of tetrafluorophenol.
  • Purify by precipitation (cold ether), dialysis (MWCO >3 kDa), or SEC, depending on ligand size and solubility.

• Notes

  • Avoid excess strong nucleophiles (thiols, hydroxyls) unless specifically targeted; they can compete with amine coupling.
  • Steric hindrance near primary amines diminishes rates; consider spacered amines or longer reaction times.

Reaction Conditions

The following are general literature-guided conditions for TFP-ester amide couplings, to be optimized per substrate. They are not item-specific specifications.

• Anhydrous coupling (typical)

  • Solvent: dry DMF or DMSO (optional CH2Cl2 co-solvent for viscosity control).
  • Stoichiometry: 1.0 eq DSPE-PEG13-TFP ester; 1.2–3.0 eq primary amine; 1–2 eq DIPEA or triethylamine.
  • Temperature/time: 20–25 °C for 2–16 h; can warm to 30–35 °C for sluggish substrates.
  • Atmosphere: N2/Ar; rigorously dry glassware and molecular sieves in solution.

• Aqueous-assisted coupling (bioconjugation)

  • Buffer: HEPES or phosphate, pH 7.5–8.5; avoid amine-containing buffers (e.g., Tris).
  • Co-solvent: 10–30% DMF or DMSO to solubilize lipid–PEG and ligand.
  • Temperature/time: 4–25 °C for 1–6 h; proceed promptly to outpace hydrolysis.

• Monitoring and workup

  • Monitor by RP-HPLC (UV 215–230 and ~260–270 nm) for loss of TFP ester and appearance of conjugate; LC–MS or MALDI for mass shift.
  • Quench residual active ester with ethanolamine or glycine, if needed.
  • Purify by precipitation (cold ether/acetone), dialysis, or SEC depending on ligand size/solubility.

• Expected outcomes (literature)

  • Near-quantitative conversions are common with unhindered primary amines under dry conditions; in mixed aqueous media, yields depend on kinetics vs hydrolysis and may require excess amine.

• Special notes

  • Avoid thiol-rich conditions unless trapping is intended; TFP esters can acylate thiols.
  • Maintain temperatures above DSPE Tm for post-insertion into bilayers after conjugation.

Safety and Handling

• GHS/SDS information for this item

  • Signal word: Not specified for this item; refer to SDS.
  • Hazard statements, pictograms, classification: Not specified for this item; refer to SDS.

• General safety considerations for TFP-activated esters (literature/guidance)

  • Reactivity: TFP esters are moisture-sensitive; hydrolysis yields tetrafluorophenol (acidic) and the corresponding carboxylate, reducing coupling efficiency. Handle under dry, inert conditions.
  • Irritation: Activated esters and fluorinated phenols may cause skin/eye/respiratory irritation. Avoid inhalation of dust/aerosols.
  • Sensitization: Reagents that acylate amines can potentially sensitize. Minimize skin contact.

• PPE and handling

  • Wear lab coat, nitrile gloves, and safety glasses; upgrade to splash goggles and chemically resistant gloves for bulk operations.
  • Work in a fume hood; avoid exposure to moisture. Use anhydrous tools/solvents; keep containers tightly closed under dry inert gas.

• Incompatibilities (general)

  • Aqueous base and nucleophiles (amines, alcohols) promote hydrolysis/transesterification; avoid unless intentionally conjugating.
  • Strong oxidizers and strong acids/bases may degrade lipid/PEG components.

• First aid (overview; defer to SDS)

  • Skin/eyes: Rinse with water for ≥15 min; remove contaminated clothing.
  • Ingestion/inhalation: Seek medical attention; move to fresh air.

• Waste

  • Collect organic waste containing fluorinated phenols separately per institutional guidelines; label as halogenated organic waste.

Always consult the product’s SDS for authoritative, lot-specific hazard and response information.

Solvent Selection

• Polarity/miscibility profile (general)

  • Amphiphilic macromolecule: soluble in chloroform, dichloromethane, and polar aprotic solvents (DMF, DMSO). Dispersible in water but TFP ester hydrolyzes; use minimal aqueous content during conjugation unless rapid coupling is ensured.

• Choosing solvents by task

  • Film formation and lipid blending: chloroform or chloroform:methanol (9:1) for thin-film hydration; remove solvent thoroughly to avoid residuals in vesicles.
  • Amine conjugation (anhydrous): anhydrous DMF or DMSO with base (e.g., DIPEA) for coupling to amines on ligands/polymers; optional co-solvent with CH2Cl2 to reduce viscosity.
  • Amine conjugation (aqueous-assisted): buffered aqueous media (HEPES, phosphate, pH 7.5–8.5) with 10–30% DMF/DMSO to solubilize the lipid–PEG; proceed promptly to minimize hydrolysis.
  • Post-insertion into preformed liposomes: disperse conjugate in warm buffer or ethanol/aqueous mixtures below critical disruptive concentrations, incubate above DSPE Tm to insert.

• Comparison to alternatives (general)

  • TFP vs NHS esters: TFP esters exhibit slower hydrolysis and improved performance in partially aqueous media; thus, they tolerate slightly higher water content during coupling.
  • Greener choices: Where feasible, replace DCM with ethyl acetate or 2-MeTHF for film dissolution; for conjugation, aqueous buffers with minimal DMF are preferable when substrate solubility allows.

• Practical tips

  • Dry solvents over molecular sieves; verify water content (KF) for sensitive work.
  • Warm viscous solutions (30–40 °C) to aid dissolution; avoid exceeding temperatures that could accelerate hydrolysis during coupling.

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 only. (From Product Data.)

• General handling guidance for TFP esters

  • Protect from moisture; keep tightly sealed under dry inert gas (N2/Ar). Include desiccant in secondary containment.
  • Avoid repeated freeze–thaw and prolonged room-temperature exposure. Aliquot upon first opening in a dry box or under a nitrogen blanket.

• Reconstitution (general)

  • For stock solutions: Dissolve in anhydrous DMF or DMSO (e.g., 5–50 mg/mL). Optionally co-dissolve with CHCl3/DCM for film methods. Filter through PTFE (0.2 µm) if needed.
  • For aqueous use: Prepare immediately before reaction in amine-free buffer (pH 7.5–8.5) with 10–30% DMF/DMSO; proceed directly to conjugation to minimize hydrolysis.

• Stability notes

  • The TFP ester is moisture-sensitive and slowly hydrolyzes, especially at elevated temperature or basic pH. Store cold and dry to preserve activity. Avoid amine-containing buffers during storage.

• Shelf-life and specifications

  • Appearance, assay, and activity retention over time are Not specified for this item; refer to CoA/Spec Sheet.

Always consult the SDS and CoA for lot-specific handling and stability information before use.

Structure and Identity

DSPE-PEG13-TFP ester is an amphiphilic lipid–polymer conjugate bearing an activated ester for amine coupling.

• Item-specific identifiers

  • CAS: 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.
  • Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.

• Structural description (general/literature)

  • DSPE segment: 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (two C18:0 chains on glycerol; phosphoethanolamine headgroup).
  • PEG13 spacer: a polyethylene glycol chain of approximately 13 ethylene oxide repeat units (–O–CH2–CH2–)13– conferring hydrophilicity and spacing.
  • Terminal functionality: 2,3,5,6-tetrafluorophenyl (TFP) activated ester linked to the PEG terminus for efficient amide bond formation with primary amines.
  • Amphiphilic block architecture: hydrophobic DSPE anchors into lipid bilayers; hydrophilic PEG projects into aqueous phase, presenting the reactive TFP ester (prior to conjugation).

• Structural features (general)

  • Functional groups: ester (glycerides), phosphate diester, secondary amine (in DSPE headgroup, typically neutralized/linked), multiple ether oxygens (PEG), and an activated aryl ester (TFP) characterized by four ring fluorines increasing leaving-group ability.
  • Polymer/distribution note: PEG-based materials present a narrow mass distribution (Ð>1), so exact atomic-level descriptors (SMILES/InChI) for the whole conjugate are not strictly single-molecule representations.
  • 2D depiction in words: two parallel C18 alkyl chains attached to glycerol → phosphate → ethanolamine → PEG chain → aryl TFP ester at the terminus.

Synthetic Utility

• Functional handle

  • The terminal TFP ester is a high-performance acylating group for forming amide bonds with primary amines, enabling installation of diverse ligands (peptides, small molecules, dyes, polymers) onto a lipid–PEG scaffold.

• Retrosynthetic perspective (general)

  • Target DSPE-PEG–Ligand constructs can be disconnected at the terminal amide, revealing ligand–NH2 and DSPE-PEG–CO2–TFP as coupling partners. Orthogonality is high provided the ligand’s amine is the most nucleophilic site or appropriately protected.

• Selectivity and compatibility

  • Prefer primary over secondary amines; minimize competing nucleophiles (thiols, phenols). Protect lysines or N-termini selectively when conjugating peptides with multiple amines to control site of attachment.
  • Aryl TFP leaving group enhances rate at neutral–mildly basic pH; less prone to hydrolysis than NHS in mixed aqueous media, supporting bioconjugation conditions.

• Downstream processing

  • Purification by precipitation into cold ether/acetone, dialysis (MWCO matched to PEG13 mass), or SEC. Analytical confirmation via disappearance of TFP ester signals and appearance of ligand-associated resonances.

• Utility scope

  • Creation of affinity ligands on lipid nanoparticles, incorporation of FRET dyes, attachment of bio-orthogonal handles (azide/alkyne/ketone) for subsequent click or oxime chemistries, and immobilization of biomolecules on supported bilayers for biophysical assays.

Target Specificity

Not applicable. This product is a chemical reagent (lipid–PEG–TFP ester) and does not have antibody/antigen or biochemical target specificity parameters. Any “specificity” arises from the ligand installed via amide coupling, which is user-defined.