THP-PEG6-C2-Boc , CAS No.T1446868

CAS: T1446868 Cat. No.: T1446868 Fórmula: C₂₄H₄₆O₁₀ Peso molecular: 494.62

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Descripción general

THP-PEG6-C2-Boc is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs.

Specifications

Condiciones de almacenamiento de almacenamiento

Store at -20°C

Enviado en

Ice chest + Ice pads

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Nombres e identificadores

• Peso molecular: 494.62

Application Protocols

No tested bioassay applications (e.g., WB, IHC, IF, FC) are provided for this small-molecule linker.

General laboratory protocol pointers (literature-level, not item-specific):

• Deprotection sequence planning: Choose whether to unmask the THP-protected alcohol or the Boc-protected amine first, based on the stability of your substrate/partner.
• Analytical monitoring: Use LC-MS with ammonium buffers for improved PEG peak shape. For TLC, use DCM/MeOH (0–10% MeOH) with ninhydrin staining for amines (post-Boc removal).
• Conjugation pilot: Perform 1–5 µmol scale couplings to optimize stoichiometry, base, and time before scaling.

For any validated, application-specific instructions, consult the CoA/Spec Sheet or contact Aladdin Scientific technical support.

Biological Roles

This product is intended for research use as a synthetic linker. It is not a biological metabolite or signaling molecule per se.

General context (literature):

• PEG segments confer hydrophilicity and reduce nonspecific interactions (antifouling). In bioconjugation, PEG spacers can enhance solubility and decrease aggregation of biomolecule–small molecule conjugates.
• The Boc-protected amine can be unveiled to a primary amine, frequently used to couple to activated carboxyl groups of proteins (e.g., via NHS esters) or to functionalize nanoparticles and surfaces.
• THP deprotection reveals a hydroxyl group that can be further derivatized to aldehydes (for oxime/Schiff base formation post-oxidation) or to electrophiles/nucleophiles enabling orthogonal attachment strategies.

Caveats:

• PEG linkers can attenuate binding by increasing spatial separation; while often beneficial, spacer length should be optimized empirically for each target system.
• No intrinsic biological activity or target engagement should be assumed for this linker. Any biological effects observed typically arise from the payload or conjugated partner, not the PEG chain itself.

Compliance note: For research use only. Not for use in diagnostic procedures or in humans/animals.

Buffer Applications

This material is a synthetic linker, not a buffering agent. It does not constitute a defined acid/base pair for pH control.

Practical notes (general):

• During deprotection or conjugation, it may be used in organic or mixed aqueous–organic media buffered to protect biomolecules (e.g., phosphate, HEPES, or bicarbonate buffers). The buffer choice depends on the functional groups exposed after deprotection and the coupling chemistry employed.
• For amide couplings with exposed amines to carboxylates on biomolecules, mild pH 7.2–8.5 buffers (PBS, HEPES, or carbonate) are typical. Avoid buffers containing primary amines (e.g., Tris) when activating carboxylates, as they can compete in coupling.

No item-specific buffer recipes or pKa values are provided; refer to your reaction protocol and the CoA/SDS for compatibility guidance.

Green Alternatives

From a green chemistry perspective, the linker functionality is typically fixed, but solvent and reagent choices can be optimized.

Greener choices (literature/general):

• Solvents:
  • Replace DCM/CHCl3 with EtOAc, 2-MeTHF, CPME, or Me-THF/DCM mixtures when feasible, especially for extractions and chromatographic elution.
  • Favor MeCN, EtOAc, or water/MeCN for LC, and ethanol or isopropanol as protic alternatives to methanol where compatible.
• Coupling reagents:
  • Consider DMTMM or CDI as alternatives to carbodiimides + HOBt/HOAt (reduces explosive/energetic by-product risk). OxymaPure with EDC/HATU lowers hazardous by-products relative to HOBt.
• Deprotection:
  • Boc removal with TFA generates acidic waste; micro-scale TFA with in situ scavengers (triisopropylsilane, water) and immediate neutralization reduces environmental load. HCl/dioxane or gaseous HCl in greener solvents (EtOAc) can be alternatives.
  • THP deprotection under catalytic PPTS in ethanol (or aqueous ethanol) is milder and more benign than strong mineral acids in chlorinated solvents.

Trade-offs:

• Greener solvents may alter solubility of PEG linkers; co-solvent systems (2-MeTHF/EtOH or EtOAc/DMF) often restore performance.
• Some “green” reagents can lead to slower kinetics or lower conversions—optimize stoichiometry and temperature accordingly.

Recommendation: Evaluate process mass intensity (PMI) by piloting greener solvent systems, and validate impurity profiles via LC-MS to ensure no new by-products are introduced.

Pharmaceutical Uses

No pharmacopeial status or excipient designation is provided for this item.

General formulation context (literature):

• PEG linkers are widely used in discovery-stage conjugates (e.g., linker–payload constructs, surface PEGylation) to modulate solubility and spacing. However, this product is supplied for research use only and is not intended for manufacturing or clinical applications.
• If translated toward regulated environments, typical considerations include residual solvent limits (ICH Q3C), elemental impurities (ICH Q3D), identity/purity (ICH Q6A), and stability-indicating methods. None of these parameters are specified here for this item.

Note: Avoid implying therapeutic effect. This product should be used strictly for laboratory research and method development.

Physical Properties

Item-specific physical properties were not provided. Do not treat the following as specifications; they are general expectations for PEG-based linkers and must be verified experimentally.

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight (calculated): Not specified for this item; refer to CoA/Spec Sheet.
• Melting point: Not specified for this item; refer to CoA/Spec Sheet.
• Boiling point: Not applicable/rarely reported for oligomeric PEG linkers; decomposition may occur (literature, general).
• Density: Typically ~1.1–1.2 g/mL for PEG oligomers (literature, general); Not specified for this item.
• Solubility (literature, general):
  • Highly soluble in polar aprotic solvents (DMF, DMSO, NMP) and many chlorinated solvents (DCM, CHCl3).
  • Moderately to highly soluble in MeOH/EtOH; limited in nonpolar hydrocarbons (hexanes).
  • Miscible with water is variable for PEG6; terminal hydrophobes (THP, Boc) can reduce aqueous solubility.
• LogP: PEG chains lower logP; end-groups increase it. No item-specific value.
• Refractive index: Not specified for this item; refer to CoA/Spec Sheet.
• pKa: Not directly applicable; Boc-amine is masked; THP ether lacks measurable acidity under neutral conditions (literature, general).

Note: Exact numerical values (UV cutoff, water/peroxide content, residual metals) are Not specified for this item; refer to CoA/Spec Sheet.

Quality and Grades

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

Context for professional users (general guidance):

• Research grade PEG linkers are typically supplied at high chemical purity (e.g., ≥95% by HPLC/UPLC) with controlled residual solvents and water. However, without item-specific data, these cannot be assumed here.
• Stabilizers: None indicated. In absence of stabilizers, protect from moisture and acids to preserve THP and Boc functionalities.
• Documentation: For mission-critical work (e.g., conjugation efficiency, regulatory filings), request the CoA including assay/purity method, residual solvents (ICH Q3C), water (Karl Fischer), and identity (NMR/HRMS). If UV transparency is relevant (e.g., photolabile steps), ask for UV-Vis trace.

What the grade implies (general):

• Analytical reagent (AR) or ≥X% purity grades indicate suitability for synthetic use with minimal by-products. HPLC-grade refers to solvents; for linkers, HPLC purity is an analytical measure—not a solvent grade.
• Low peroxide content can be important for PEG reagents, as peroxides may accumulate in some ethers; no item-specific limits are provided here.

Recommendation: Verify compatibility and performance in a small-scale pilot conjugation, and confirm purification profile (e.g., LC-MS) before scale-up.

Reaction and Applications

The THP-PEG6-C2-Boc motif is characteristic of a heterobifunctional PEG linker enabling orthogonal transformations at each terminus.

General application scenarios (literature/context; not item-specific guarantees):

• Sequential deprotection strategy:
  • THP removal (acid-catalyzed) reveals a terminal alcohol, which can be oxidized (e.g., Dess–Martin, TEMPO/BAIB) to an aldehyde/carboxylate for conjugation, or converted to a leaving group (tosylate/mesylate) to introduce other handles (azide, halide).
  • Boc deprotection (TFA, HCl/dioxane) liberates a primary amine for amide coupling (EDC/HOBt, HATU, PyBOP), urea formation (with isocyanates), or reductive amination to carbonyl partners.
• Spacer role: PEG6 provides ~2.6–3.0 nm end-to-end reach in solution (literature estimate), improving solubility and reducing steric hindrance in bioconjugations (proteins, surfaces, nanoparticles).
• Surface/solid support modification: After unmasking appropriate termini, the linker can graft onto carboxylated, aminated, or hydroxylated surfaces, aiding antifouling and distance control.
• Click chemistry preparation: Converting the alcohol end to azide (via tosylate→azide) generates an azido-PEG-Boc amine precursor for CuAAC or SPAAC once the complementary alkyne/cyclooctyne is available.

Practical tips:

• Work under anhydrous conditions for coupling steps; moisture impairs carbodiimide and uronium chemistries.
• Monitor deprotections by LC-MS; PEG distributions can broaden peaks—use evaporative light-scattering or MS detection.
• Purification: Silica gel tolerates PEGs, but use minimal polar eluents (DCM/MeOH with 0.5–2% NH3 for amines) or resort to reverse-phase prep-HPLC for cleaner separations.

Reaction Conditions

Typical conditions for transformations relevant to a THP- and Boc-protected PEG linker (literature guidance; verify on small scale):

• THP deprotection (to alcohol):
  • PPTS (5–10 mol%) in EtOH or MeOH, 0–25°C, 1–6 h. Alternatively, 1–5% HCl(aq)/THF–H2O (9:1) at 0–25°C. Monitor by TLC/LC-MS.
• Boc deprotection (to amine):
  • TFA:DCM (1:1 to 1:9 v/v), 0–25°C, 0.5–2 h, with scavengers (H2O, TIPS). Or 4 M HCl/dioxane, 0–25°C, 1–3 h.
• Alcohol oxidations (after THP removal):
  • Dess–Martin periodinane (1.3 eq), DCM, 0–25°C, 0.5–2 h → aldehyde.
  • TEMPO/BAIB or TEMPO/NaOCl (pH 8–9), 0–10°C → aldehyde/acid.
• Alcohol activation/substitution:
  • MsCl (1.2 eq), Et3N, DCM, 0–5°C → mesylate; then NaN3 (2–5 eq) in DMF, 60–80°C → azide.
• Amide coupling (after Boc removal to amine):
  • HATU (1.1–1.5 eq), DIPEA (2–3 eq), DMF, 0–25°C, 1–4 h with carboxylic acids.
  • EDC·HCl (1.2 eq) + Oxyma (1.2 eq), DIPEA, DMF or MeCN, 25°C, 2–16 h.

Yields: Strongly substrate-dependent; PEGylated systems often give 60–90% in clean couplings under optimized conditions (literature range). Always confirm by LC-MS/NMR.

Notes:

• Protect from strong acids during non-deprotection steps to preserve THP/Boc.
• Control moisture; pre-dry reagents/solvents. PEG chains can sequester water.
• Workup: Partition between water and EtOAc/MTBE; add brine to break emulsions often formed by PEGs.

Safety and Handling

Authoritative safety information depends on the SDS. The following are general considerations for PEGylated, acid-labile protected linkers.

• GHS classification, signal word, pictograms, H-statements: Not specified for this item; refer to SDS.
• Likely hazards (general): Organic linkers may cause skin/eye irritation and respiratory tract irritation as dust or vapors. Acid-labile groups (THP, Boc) can generate isobutylene/CO2 (Boc deprotection) or hemiacetals under strong acid.
• PPE: Use lab coat, safety glasses, and appropriate chemically resistant gloves (e.g., nitrile). Handle powders in a fume hood to minimize inhalation.
• Incompatibilities (general):
  • Strong acids promote cleavage of THP ethers and Boc carbamates; avoid accidental exposure unless deprotection is intended.
  • Strong oxidizers and strong bases can degrade PEG backbones over time.
  • Moisture can accelerate acid-catalyzed acetal hydrolysis.
• First aid (general):
  • Skin/eye contact: Rinse with water for at least 15 minutes; remove contaminated clothing; seek medical attention as needed.
  • Inhalation: Move to fresh air; seek medical evaluation if symptoms persist.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Fire safety: Treat as a combustible organic solid. Use CO2, dry chemical, or foam. Thermal decomposition may produce CO/CO2 and other irritants.
• Waste: Collect as organic chemical waste per institutional/municipal regulations.

Always consult the product-specific SDS for definitive hazard classifications and response measures.

Solvent Selection

Solvent choice for THP-PEG6-C2-Boc should balance PEG solvation and protection-group stability.

• Polarity/miscibility (literature, general):
  • Readily soluble in polar aprotics (DMF, DMSO, NMP) and likely in DCM/CHCl3 due to Boc/THP termini.
  • Solubility in MeOH/EtOH is typically good; aqueous solubility may be modest due to hydrophobic end-groups.
• Avoid prolonged exposure to strong acids in protic media (e.g., TFA/MeOH) unless deprotection is intended; THP and Boc are acid-labile.
• Drying: Use anhydrous solvents when performing moisture-sensitive couplings (e.g., carbodiimide or NHS ester chemistry after functional group unmasking).

Comparison (general considerations):

• DCM vs DMF: DCM ideal for Boc deprotection and workups; DMF preferred for amide couplings after Boc removal due to higher polarity and solubilization of bases/activators.
• THF/2-MeTHF: Can dissolve PEG linkers but may require co-solvent with DMF for coupling reagents; ethers can form peroxides on storage—monitor and use inhibitors as appropriate.
• Aqueous-organic systems: Following deprotection and derivatization, PEG segments can aid phase transfer; mixed DMF/H2O or MeCN/H2O systems may be used for bioconjugation on biomolecules.

Practical tip: Start with DCM, DMF, or DMSO (anhydrous) test dissolutions at ~10–50 mg/mL, then adjust co-solvent composition based on the downstream chemistry.

Storage and Reconstitution

Item-specific storage and shipping:

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

General handling guidance for this class of linkers:

• Keep container tightly closed under inert atmosphere (argon/nitrogen) when possible. Protect from moisture and strong acids to preserve THP and Boc groups.
• Minimize freeze–thaw cycles; dispense into small aliquots upon first opening.
• Light sensitivity is typically low, but opaque containers help reduce degradation of sensitive protecting groups.

Reconstitution (general suggestions; verify experimentally):

• Dissolve in anhydrous organic solvents such as DCM, DMF, or DMSO. Typical working stocks: 10–100 mM depending on downstream chemistry.
• For bioconjugation in aqueous systems, prepare a concentrated stock in DMF or DMSO and add to the aqueous phase with vigorous mixing; keep final organic content compatible with the biomolecule (<10–20% v/v commonly used).
• If solids persist, gentle warming (25–35°C) and sonication can aid dissolution; avoid elevated temperatures during extended periods to prevent degradation.

Stability testing: For long projects, confirm integrity periodically by LC-MS/NMR, especially after storage >6 months or repeated handling.

Structure and Identity

Item-specific identifiers provided: minimal. Where an identifier is not given below, consult the CoA/Spec Sheet.

• SKU: T1446868 (Aladdin Scientific)
• Product name: THP-PEG6-C2-Boc
• 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 interpretation from name (general/literature context, not an item-specific specification):

• THP denotes a 2-tetrahydropyranyl protecting group, typically capping a terminal alcohol as a THP ether; it is acid-labile.
• PEG6 indicates a hexaethylene glycol spacer (–[CH2CH2O]6–) imparting hydrophilicity and flexibility.
• C2 suggests a short two-carbon linker segment bridging to the terminal functionality.
• Boc indicates a tert-butyloxycarbonyl-protected amine (–NH–Boc), base-stable and acid-labile.
• Overall, the name is consistent with a heterobifunctional PEG linker bearing a THP-protected hydroxyl at one end and a Boc-protected amine at the other, useful for sequential deprotection and conjugation.

2D structural features (literature-style description):

• A polyether backbone (six ethylene oxide repeats) between two termini: one side an acetal (THP ether) linked to an oxygen; the other side a carbamate (Boc) attached to a primary amine via a short alkyl chain (C2). No stereocenters are expected in the PEG region; the THP ring contains multiple C–O/C–C single bonds.

Synthetic Utility

Functional group strategy (general, based on name-derived features):

• THP-protected alcohol terminus:
  • Deprotect under mild acid (PPTS, dilute HCl, or TFA in controlled amounts) to reveal a primary alcohol.
  • Transformations: oxidation to aldehyde/carboxylic acid (Dess–Martin, TEMPO/NaOCl/NaClO2), activation as sulfonate (MsCl/TsCl) then substitution (e.g., to azide → Staudinger/Traceless Staudinger, CuAAC after alkyne installation), or carbonate/urethane formation.
• Boc-protected amine terminus:
  • Deprotect with TFA or HCl/dioxane to the free amine.
  • Transformations: amide (EDC/Oxyma, HATU), urea (with CDI-activated amines/isocyanates), thiourea (isothiocyanates), or reductive amination.

Value in retrosynthesis:

• Provides a hydrophilic, flexible spacer (PEG6) that can reduce intramolecular interactions and improve solubility of conjugates, facilitating purification (RP-HPLC compatibility) and handling.
• Orthogonality of protecting groups enables stepwise assembly—choose which end to unmask first based on substrate stability.

Operational considerations:

• Use anhydrous conditions for coupling; PEG chains can retain water—pre-dry by azeotrope with toluene or co-evaporate with dry acetonitrile.
• Monitor reactions by LC-MS; sodium/potassium adducts are common for PEGs—add ammonium formate/acetate for MS-friendly conditions.
• Purification: Reverse-phase methods (C18, water/MeCN + 0.1% formic acid or NH4HCO3) often give better resolution of PEGylated species than normal-phase.

Target Specificity

Not applicable. This product is a small-molecule linker and does not have biological target specificity, antigen/epitope details, or antibody clone/isotype information. No item-specific target data are provided.