VH 032 amide-PEG2-alkyne - ≥95%(HPLC) , CAS No.2098799-80-3

CAS: 2098799-80-3 Cat. No.: V287666 Summenformel: C₃₁H₄₂N₄O₇S Molekulargewicht: 614.75 PubChem CID: 132045744

QUALITÄT & REINHEIT ≥95%(HPLC)

Synonyms

VH 032 - linker 6 | (2S,4R)-1-((S)-2-(tert-Butyl)-4-oxo-6,9,12-trioxa-3-azapentadec-14-yn-1-oyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide | VH032-PEG3-acetylene

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Spezifikationen

Synonyme

VH 032 - linker 6 | (2S,4R)-1-((S)-2-(tert-Butyl)-4-oxo-6,9,12-trioxa-3-azapentadec-14-yn-1-oyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide | VH032-PEG3-acetylene

Spezifikationen & Reinheit

≥95%(HPLC)

Storage

Store at -20°C

Verschickt in

Ice chest + Ice pads

Dieses Produkt erfordert Kühlkettenversand. Grundversand und andere Economy-Optionen sind nicht verfügbar.

Reinheit

≥95%(HPLC)

Namen und Kennungen

Pubchem Sid

488202765

Pubchem Sid Url

https://pubchem.ncbi.nlm.nih.gov/substance/488202765

Kanonisches Lächeln

CC1=C(SC=N1)C2=CC=C(C=C2)CNC(=O)C3CC(CN3C(=O)C(C(C)(C)C)NC(=O)COCCOCCOCC#C)O

IUPAC Name

(2S,4R)-1-[(2S)-3,3-dimethyl-2-[[2-[2-(2-prop-2-ynoxyethoxy)ethoxy]acetyl]amino]butanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide

InChIKey

HHXQNDSXTCIWSG-CERRFVOPSA-N

INCHI

1S/C31H42N4O7S/c1-6-11-40-12-13-41-14-15-42-19-26(37)34-28(31(3,4)5)30(39)35-18-24(36)16-25(35)29(38)32-17-22-7-9-23(10-8-22)27-21(2)33-20-43-27/h1,7-10,20,24-25,28,36H,11-19H2,2-5H3,(H,32,38)(H,34,37)/t24-,25+,28-/m1/s1

PubChem CID

132045744

Molekulargewicht

614.75

Application Protocols

No vendor-validated experimental application protocols are provided for this item. As a small-molecule building block, it is typically used in synthetic organic chemistry rather than in direct assay formats.

General workflow guidance (literature/general):

• Stock preparation: Dissolve in anhydrous DMSO to a convenient concentration (e.g., 10–50 mM) for library synthesis; filter through 0.2 µm PTFE.
• CuAAC assembly: Combine azide partner (1.0–1.2 eq), this alkyne (1.0 eq), CuSO4 (5–10 mol%), sodium ascorbate (10–20 mol%), and a ligand (e.g., THPTA) in t-BuOH/H2O (1:1). Stir at rt to 40°C until LC–MS indicates completion. Chelate and remove copper, then purify.
• Characterization: Confirm product by LC–MS, HRMS, and 1H/13C NMR; assess purity by HPLC. For VHL-binding modules, verify stereochemical integrity where relevant.

Note: The above are general literature-style procedures and should be optimized for your specific substrates and scale. Always consult the SDS and CoA for item-specific handling and characterization details.

Biological Roles

• Context (literature/general; no therapeutic claims)

  • VH032 is a synthetic ligand that binds the von Hippel–Lindau (VHL) E3 ubiquitin ligase complex by mimicking hydroxyproline-containing HIF-1α motifs. It is widely used as the E3 ligase-recruiting half of heterobifunctional degraders (PROTACs).
  • The PEG2-alkyne appendage does not confer biological activity itself; rather, it serves as a conjugation handle to attach a ligand for a protein of interest, generating a bifunctional molecule capable of ternary complex formation (target–PROTAC–VHL) and subsequent ubiquitination of the target.

• Biochemical considerations

  • Stereochemistry at the hydroxyproline of VH032 is critical for VHL binding; epimerization or racemization can abolish affinity.
  • Linker composition and length (PEG2 here) affect ternary complex stability and cell permeability of resultant conjugates; PEG segments increase polarity and aqueous compatibility but may reduce passive permeability.
  • The terminal alkyne enables modular assembly via CuAAC, providing a triazole linkage that is metabolically robust and often tolerated in protein–ligand interfaces.

• Use in research systems

  • Employed to probe ubiquitin–proteasome pathway function by assembling chemical degraders and studying structure–activity relationships of linkers and exit vectors from the VHL ligand.

Note: This catalog item is for research use only.

Buffer Applications

This product is not a buffering reagent and is not typically employed to prepare analytical or biological buffers. For experimental use, it is usually dissolved in organic solvents (e.g., DMSO, DMF) and then introduced into reaction media or assay systems at low percentages of co-solvent. If aqueous compatibility is required for a conjugation step (e.g., CuAAC), mixed aqueous–organic solvent systems such as t-BuOH/H2O or EtOH/H2O can be used as reaction media (literature guidance), but the compound does not itself define buffer capacity or pH.

For buffer selection related to assays of conjugates made from this building block, choose buffers based on the biological target and technique (e.g., PBS, HEPES, Tris), ensuring compatibility with any residual copper from click reactions (include chelators like EDTA where appropriate).

Green Alternatives

• Solvent and methodology choices (literature/general; evaluate for your system)

  • Greener solvents for CuAAC:
    • t-BuOH/H2O or EtOH/H2O mixtures can replace DMF/DMSO in many click reactions, reducing solvent hazard and easing workup.
    • 2-MeTHF/H2O is an additional option with better renewability than some dipolar aprotics.
  • Copper source/ligands:
    • Use catalytic CuSO4/sodium ascorbate with water-compatible ligands (e.g., THPTA) to minimize copper loading and facilitate aqueous workups.
  • Copper-free alternatives:
    • If compatible with the project, SPAAC (strain-promoted azide–alkyne cycloaddition) using a strained cyclooctyne warhead avoids copper entirely; this would require the complementary partner to carry the strained alkyne and this reagent to be azide-bearing, so it is an alternate design rather than a condition change.

• Small comparison (general)

  • DMF/DMSO: high performance, but problematic for EHS and removal.
  • t-BuOH/H2O or EtOH/H2O: greener profile, simple removal, often similar kinetics with proper ligand.
  • 2-MeTHF: bio-based option; may require cosolvent for highly polar VH032 derivatives.

• Waste minimization

  • Run reactions at higher concentration where feasible.
  • Implement aqueous workups that chelate/remove copper efficiently (e.g., EDTA wash) to reduce metal in organic waste.

Pharmaceutical Uses

This item is a research-grade small-molecule building block for chemical biology and medicinal chemistry and is not an excipient or GMP material. It does not have a defined role in pharmacopeial formulations.

• Research/manufacturing context (general)

  • Used in discovery-phase synthesis of bifunctional molecules (e.g., PROTACs) to explore structure–activity relationships. Resulting conjugates may be evaluated in biochemical/cellular assays under research-use-only conditions.
  • The PEG2 linker and terminal alkyne facilitate modular assembly and solubility tuning during lead identification.

• Considerations if transitioning to development (general guidance, not specific to this item)

  • For preclinical development, GMP-grade synthesis, full impurity profiling, residual metal analysis, and stability-indicating methods would be required for any derived clinical candidate, not for this building block.
  • Replacement of laboratory solvents (DMF, DMSO) with ICH-preferred solvents and establishment of acceptable residual limits would be needed.

No therapeutic or clinical claims are made for this product. It is supplied strictly for research use only.

Physical Properties

• Item-specific (Product Data)

  • 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.

• Literature/general expectations for this class (VH032–PEG2–alkyne derivatives; not specifications)

  • Physical state: typically an off-white to white solid for analogous VH032-PEGn derivatives.
  • Solubility: commonly soluble in polar aprotic organic solvents (DMSO, DMF, DMAc) and mixed aqueous-organic media with co-solvent; limited solubility in nonpolar hydrocarbons due to PEG and amide content.
  • Acid/base behavior: predominantly neutral; contains amide(s) and alcohol; terminal alkyne has mildly acidic proton (pKa for terminal alkynes often ~24–26 in DMSO, literature), not appreciably deprotonated in water.
  • Partitioning: PEG units decrease lipophilicity relative to purely hydrocarbon linkers; overall logP for related VH032-linker conjugates tends to be moderate, but is sequence/linker-length dependent (literature).
  • Thermal behavior: PEGylated amide solids often show broad melting events; avoid overheating to prevent degradation.
  • Spectroscopy: UV absorbance primarily from amide/peptide backbone and any aromatic moieties present in VH032 core; no defined UV cutoff like HPLC solvents.

For exact numerical values (mp, bp, density, refractive index, water content), consult the CoA/Spec Sheet for this lot.

Quality and Grades

• Item-specific (Product Data)

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

• Interpretation and expectations (general)

  • For heterobifunctional PROTAC building blocks such as VH032–PEG2–alkyne, typical quality criteria include:
    • High chemical purity (often ≥95% by HPLC for synthetic applications), low related impurities to avoid side-product formation during coupling/click steps.
    • Clear characterization: 1H/13C NMR, HRMS, and LC–MS retention time/purity traces. Where applicable, chiral integrity at the VH032 stereocenters verified by optical rotation or chiral HPLC.
    • Residual solvent and water content documented by GC/HSGC and Karl Fischer; important for moisture-sensitive couplings.
    • Metal content: low residual Pd/Cu/Ni if used in synthesis; critical when subsequent reactions are metal-catalyzed.
  • Stabilizer/additives: None are typically required; if any are used, they should be disclosed on the CoA. For terminal alkynes, absence of copper is generally preferred at point of use.
  • What the grade means:
    • “Research grade” or “synthetic grade” generally indicates suitability for organic synthesis and library construction, but not GMP or clinical manufacture.

Refer to the CoA/Spec Sheet for this specific item’s purity assay, chromatographic method, and analytical data.

Reaction and Applications

• Primary application (literature/general)

  • This reagent is a PROTAC building block: a VHL (VH032) ligand equipped with an amide-linked PEG2 spacer terminating in a terminal alkyne for azide–alkyne cycloaddition (CuAAC) to append a target-binding warhead or reporter.

• Typical reaction families

  • Copper-catalyzed azide–alkyne cycloaddition (CuAAC): forms 1,4-disubstituted triazoles efficiently under mild conditions with catalytic Cu(I) or in situ Cu(II)/ascorbate.
  • Amide coupling: the “amide-PEG2” junction on the VH032 side is already present; further amide formation may be performed on other handles if present in the partner molecule.
  • Protecting-group manipulations: VH032 cores sometimes bear protecting groups during multistep assembly; ensure deprotections are compatible with the alkyne.

• Practical tips

  • Use freshly prepared copper(I) sources or generate Cu(I) in situ (CuSO4 + sodium ascorbate) and include chelating ligands (e.g., TBTA, THPTA) to accelerate CuAAC and suppress alkyne oxidative dimerization.
  • Minimize exposure of the terminal alkyne to strong base; if acetylide formation is required for specific transformations, strictly anhydrous conditions are needed.
  • For library synthesis, weigh into vials under dry atmosphere and prepare DMSO stocks at known concentration; track equivalents carefully to ensure complete consumption of limiting partner in click steps.
  • Analytical follow-up: LC–MS monitoring of the disappearance of the alkyne (characteristic mass shift upon triazole formation) and purity of conjugates.

Reaction Conditions

• CuAAC (literature general guidance; adjust to your substrate set)

  • Solvent: t-BuOH/H2O (1:1) or EtOH/H2O mixtures; alternatively DMF/H2O or DMSO/H2O for poorly soluble partners.
  • Catalyst: CuSO4·5H2O (5–10 mol%) with sodium ascorbate (10–20 mol%) to generate Cu(I) in situ; optional ligand THPTA or TBTA (5–10 mol%) to accelerate and suppress side reactions.
  • Temperature/time: 20–40°C, 0.5–16 h depending on substrate and concentration.
  • Concentration: 5–50 mM typical; higher concentration can increase rate but monitor for precipitation.
  • Workup: Aqueous EDTA wash to chelate copper; extract with EtOAc or 2-MeTHF; purify by flash chromatography or preparative HPLC as needed.

• Amide couplings involving complementary partners (general)

  • Coupling agents: HATU, HBTU, COMU, or EDCI/Oxyma; base such as DIPEA or NMM in DMF/DMAc (anhydrous).
  • Temperature: 0–25°C start; allow to warm if needed. Typical times 1–12 h.
  • Additive control: For sensitive stereocenters on VH032, minimize time at high pH to limit epimerization.

• Side reaction control

  • Suppress Glaser homocoupling by excluding oxygen and using reductive conditions during CuAAC.
  • If base-induced acetylide formation is exploited (rare for this application), strictly anhydrous, oxygen-free conditions and copper-free setups are required.

Note: These are literature-style conditions; optimize for your substrates.

Safety and Handling

• Item-specific (Product Data)

  • GHS classification, signal word, pictograms, H-statements: Not specified for this item; refer to SDS.
  • Storage: Store at −20°C.
  • Shipping: Ice chest + ice pads (cold chain).

• General laboratory safety (literature/general guidance; defer to SDS)

  • Handle as a research chemical. Avoid inhalation of dust, and prevent contact with skin and eyes.
  • PPE: lab coat, safety glasses, and appropriate chemically resistant gloves (e.g., nitrile). Use in a fume hood during weighing and solution preparation.
  • Incompatibilities: Strong oxidizers may react with organic substrates; strong bases can deprotonate terminal alkynes forming sensitive acetylides; copper salts are intentionally used in CuAAC but avoid unintended metal contamination in storage.
  • Stability considerations: Protect from moisture and prolonged light/air exposure. PEG/amide frameworks are generally stable, while terminal alkynes can undergo oxidative homocoupling in presence of Cu/O2; store under inert atmosphere if long-term stability is critical.
  • First aid (overview; consult SDS): If on skin/eyes, rinse with water for several minutes; remove contaminated clothing. If inhaled, move to fresh air. If ingested, rinse mouth; seek medical attention in all cases of exposure.
  • Waste: Dispose according to institutional and local regulations for organic laboratory waste. Residual copper-containing reaction mixtures from click chemistry should be collected as heavy-metal waste.

Solvent Selection

• Compound class considerations (literature/general)

  • Polarity: The amide-PEG2-alkyne architecture imparts moderate polarity and hydrogen-bonding capacity. Such molecules are typically readily soluble in DMSO, DMF, DMAc, and NMP, and show improved miscibility in alcohols versus alkanes.
  • Recommended stock solutions: DMSO is commonly used to prepare stable concentrates for library synthesis and screening of conjugation reactions.
  • Aqueous handling: Solubility in pure water is often limited but can be increased with co-solvent (10–50% DMSO/DMF) or by basifying aqueous media only if compatible with other functionalities (note that strong base can generate acetylides from terminal alkynes).

• Choosing among common solvents (general guidance)

  • DMSO: excellent solvating power; good for long-term freezer stocks; high boiling point eases handling but complicates removal.
  • DMF/DMAc/NMP: ideal for amide couplings; remove under high vacuum or via co-evaporation with toluene or i-PrOH.
  • t-BuOH/H2O or MeOH/H2O: frequently used in CuAAC; tunable polarity and benign workup.
  • 2-MeTHF or EtOAc: useful for extractions/workups; limited solubility for highly polar VH032 derivatives.

• Practical tips

  • Pre-warm viscous polar solvents to aid dissolution. Filter stock solutions (0.2 µm PTFE) before use for reproducibility in microscale reactions.
  • Avoid prolonged exposure to strong base or strong oxidants during dissolution to preserve the terminal alkyne.

Storage and Reconstitution

• Item-specific (Product Data)

  • Storage conditions: Store at −20°C.
  • Shipping: Ice chest + ice pads.

• General handling guidance (not item specifications)

  • Upon receipt: Allow to equilibrate to room temperature in a desiccator before opening to prevent condensation. Reseal promptly under dry inert gas if possible.
  • Solid stability: Keep tightly capped in a dry, dark environment. Avoid repeated warming/cooling cycles; aliquot if frequent access is expected.

• Reconstitution (general practice for this class)

  • Solvents: DMSO, DMF, or DMAc typically provide rapid dissolution. For working solutions in aqueous systems, dilute DMSO stocks into buffer with vigorous mixing to final organic content ≤1–5% as compatible with your application.
  • Suggested stock concentration: Commonly 10–50 mM in DMSO for library use; select concentration based on solubility and intended dosing in reactions.
  • Filtration: Pass solutions through a 0.2 µm PTFE syringe filter to remove particulates before microplate dispensing or LC–MS analysis.

• Stability of solutions (general)

  • Store DMSO stocks at −20°C, protected from light. Use amber vials. Minimize freeze–thaw cycles by preparing aliquots. Monitor by LC–MS for degradation over time, especially if copper traces might catalyze alkyne side reactions.

Refer to the CoA/SDS for any additional item-specific storage notes.

Structure and Identity

• Item-specific (Product Data)

  • Product name: VH 032 amide-PEG2-alkyne (SKU: V287666)
  • CAS: 2098799-80-3
  • PubChem CID: 132045744
  • InChIKey: 121997 (as provided)
  • 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.

• Literature/structural interpretation (non-spec; inferred from name)

  • Core motif: “VH032” denotes a hydroxyproline-based ligand for the VHL E3 ubiquitin ligase frequently used in PROTAC design.
  • Linker: “amide-PEG2” indicates an amide connection to a short polyethylene glycol spacer of two ethylene glycol units (–O–CH2–CH2–O–CH2–CH2–), providing polarity and flexibility.
  • Handle: “alkyne” denotes a terminal acetylene (–C≡CH) for CuAAC (“click”) ligation to azides.
  • Functional groups likely present: secondary alcohol (hydroxyproline), amide(s), ether oxygens (PEG), tertiary/secondary amide linkages, terminal alkyne.

• 2D description in words (general)

  • A compact bicyclic/L-proline-derived VH032 recognition element bearing an amide that tethers a short PEG2 chain terminating in a terminal alkyne. The molecule contains multiple heteroatoms (O, N) imparting H-bonding capacity and moderate polarity, with one linear unsaturation (C≡C) at the terminus suitable for click-assembly to azides.

Note: Exact atom connectivity, stereochemistry, and indices should be confirmed against the Certificate of Analysis or a structure file for this specific catalog item.

Synthetic Utility

• Functional group handle

  • Terminal alkyne enables chemoselective ligation to organic azides via Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC), forming a stable 1,4-triazole. This permits rapid diversification with minimal protecting-group manipulation and high tolerance to functional groups.

• Ligase-recruiting module

  • The VH032 core provides a VHL-binding element, allowing the conjugate to recruit an E3 ligase in degrader designs. This greatly streamlines PROTAC assembly by separating “warhead” and “E3 ligand” synthesis.

• Linker engineering

  • PEG2 length offers a balance between flexibility and polarity. The amide-anchored PEG enables straightforward coupling strategies and predictable orientation for exit-vector optimization.

• Retrosynthetic planning (general)

  • Treat the molecule as two modules: (1) VH032-amide-PEG2–alkyne, (2) azide-bearing warhead or reporter. A single CuAAC step unites them late-stage, minimizing exposure of sensitive warheads to harsh conditions.

• Orthogonality and selectivity

  • The terminal alkyne is orthogonal to many protective groups and to common amide/ester transformations, enabling parallel synthesis. Care is needed to avoid Glaser coupling (alkyne homocoupling) under oxidative Cu conditions—use chelating ligands and reductive conditions.

• Analytics

  • Reaction progress is readily tracked by LC–MS and, where applicable, 1H NMR (disappearance of terminal alkyne proton ~2–3 ppm region in some systems; literature generalization).

Target Specificity

No target-binding selectivity data are provided for this catalog item. This product is a small-molecule building block rather than a biologic or assay-validated probe. In general literature context, VH032-based ligands bind the VHL E3 ubiquitin ligase, but any actual binding constants and selectivity for this specific item should be confirmed from primary literature or the CoA if available.

Item-specific data required for typical fields (antigen, clone, isotype, host species, species reactivity) are not applicable to this product type.

Häufig gestellte Fragen

What is the purity of this product, and how is it determined?

This product is supplied at ≥95% purity, determined by HPLC. Lot-specific values are stated on the Certificate of Analysis.

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 2098799-80-3, the molecular formula is C??H??N?O?S, and the molecular weight is 614.75 g/mol. InChIKey HHXQNDSXTCIWSG-CERRFVOPSA-N.

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.