AS1411-C4-VH032

Cat. No.: A1449874

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Übersicht

AS1411-C4-VH032 (AS1411-VH032) promotes tumor-selective degradation of MDM2 , leading to tumor shrinkage without detectable toxicity.

Specifications

Storage

Store at -20°C

Verschickt in

Ice chest + Ice pads

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

Application Protocols

• Tested applications, recommended dilutions, positive controls: Not specified for this item; refer to CoA/Spec Sheet.

• General notes:

  • Because no application protocols are provided for this item, users should optimize conditions empirically for their assay format (e.g., cell-based, biochemical, or biophysical). Include appropriate negative and positive controls and verify integrity by analytical HPLC/LC–MS where feasible.

No validated protocols are claimed for this product listing.

Biological Roles

• Item-specific biological targets/roles: Not specified for this item; refer to CoA/Spec Sheet.

• Literature context (for background only, not a product claim):

  • AS1411 is a DNA aptamer widely reported to bind cell-surface and nucleolar nucleolin, a multifunctional RNA/DNA-binding protein implicated in ribosome biogenesis and trafficking. Its G‑quadruplex structure contributes to affinity and specificity in vitro.
  • VH032 is a small-molecule ligand for the VHL E3 ubiquitin ligase complex, commonly used in the design of heterobifunctional degraders (PROTACs) for research. The hydroxyproline core engages VHL through defined H‑bond interactions (co-crystal structures in literature).
  • When combined via a linker, such entities are studied as proximity-inducing chimeras to explore targeted modulation of proteins spatially associated with the aptamer’s binding site (chemical biology research). Actual behavior depends on sequence, linker chemistry, local concentrations, and cell context.

• Experimental considerations (general):

  • Folding buffer composition (K+, Na+) affects G‑quadruplex topology and thus binding behavior of AS1411-like aptamers.
  • Serum nucleases and cellular uptake pathways can impact stability and intracellular localization; researchers often employ chemical modifications (e.g., phosphorothioates, 2′ modifications) to enhance stability—no such modifications are specified for this item.

No biological performance is claimed or implied for this specific product beyond research use only.

Buffer Applications

• Item-specific buffer instructions: Not specified for this item; refer to CoA/Spec Sheet.

• General buffer guidance for aptamer conjugates (literature-based):

  • Stock preparation: Reconstitute in nuclease‑free water or 1× PBS/HEPES (pH ~7.2–7.5). If hydrophobicity from the payload hinders dissolution, pre-wet with a small volume of DMSO, then dilute into buffer.
  • Folding: For G‑quadruplex aptamers, anneal by heating to 90–95°C for 3–5 min in desired buffer containing K+ or Na+, then slow-cool to room temperature to promote proper folding.
  • Working buffers: For cell assays, isotonic buffers (PBS) or culture media are commonly used; keep final organic solvent ≤0.5–1% v/v when possible to preserve cell health.
  • Filtration: 0.22 µm PVDF or PES filters can be used if compatible with the conjugate and concentration; avoid excessive shear or adsorptive losses.

• Additives and stability (general):

  • Avoid strong chelators or high divalent cation concentrations unless required, as they may affect structure or promote aggregation.
  • Include nuclease inhibitors or work at low temperature to mitigate degradation during extended handling.

These are general practices only; definitive buffer and preparation instructions for this item are not specified here.

Green Alternatives

• Context:

  • As a conjugate likely intended for aqueous biological assays, the principal environmental consideration is minimizing hazardous organic solvents and avoiding halogenated waste.

• Greener handling strategies (general guidance):

  • Prefer aqueous buffers (PBS, HEPES) as primary vehicles; use the lowest feasible DMSO percentage consistent with solubility and assay performance.
  • Avoid chlorinated solvents (e.g., DCM, chloroform) for any preparative steps post-receipt; reserve them only for analytical extractions if absolutely necessary.
  • Employ micro-scale assays to reduce overall chemical usage and waste.
  • Choose nuclease-free, low‑binding plastics; consolidate washes to minimize buffer waste while maintaining data quality.

• Comparison (literature-based, not item-specific):

  • Using water/PBS vs. DMF or MeCN as the main solvent substantially reduces VOC emissions and hazard classification of waste streams.
  • For LC–MS characterization, water/MeCN with volatile additives (e.g., formic acid) is preferable to non-volatile buffer salts, improving compatibility with solvent recycling.

• End-of-life and waste:

  • Most aqueous solutions can be disposed of according to institutional guidelines for non-hazardous biological/chemical waste if free from toxic additives; always follow local regulations and your EHS office’s instructions.

These recommendations are general green-chemistry practices for handling nucleic acid conjugates and are not specifications of the product.

Pharmaceutical Uses

• This catalog item is designated For research use only. It is not intended for human or veterinary use, diagnostics, or as a drug substance/product.

• Pharmacopeial status and excipient roles: Not specified for this item; refer to CoA/Spec Sheet.

• General formulation context (non-clinical, research):

  • In preclinical research, nucleic acid–small molecule conjugates are often prepared in sterile, nuclease‑free buffers for in vitro or ex vivo studies. Researchers may explore stabilizing modifications or carriers (e.g., sugars, salts), but such details are outside the scope of this product listing and are not specified.
  • Filtration through 0.22 µm membranes and storage in depyrogenated vials can reduce bioburden for laboratory experiments; this does not imply sterility for clinical use.

No therapeutic, diagnostic, or clinical claims are made for this product.

Physical Properties

• Item-specific values (specification):

  • Appearance: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
  • Solubility: Not specified for this item; refer to CoA/Spec Sheet.
  • Melting point, boiling point, density, refractive index, logP, pKa: Not specified for this item; refer to CoA/Spec Sheet.

• General/literature context for aptamer–small molecule conjugates (not product specifications):

  • Physical state: Often provided as a lyophilized solid or frozen aqueous aliquot for nucleic acid conjugates.
  • Solubility: The oligonucleotide domain typically confers high water solubility (buffered saline, nuclease‑free water). When hydrophobic payloads are appended, modest proportions of DMSO may be used for pre-wetting before dilution into aqueous buffers.
  • pH sensitivity: G‑quadruplex aptamers generally remain stable in near‑neutral buffers (pH ~6.5–8.0), with cation concentration (K+, Na+) influencing quadruplex folding (literature).
  • Ionic requirements: Folding and stability may depend on monovalent cations; Mg2+ can affect structure and nuclease susceptibility (literature).

• Practical notes (general):

  • If supplied lyophilized, reconstitute with nuclease‑free water or buffer to a convenient stock concentration (e.g., 100–1000 µM), then aliquot to minimize freeze–thaw.
  • Avoid strong acids/bases and oxidative conditions that may degrade nucleotides or amide linkages.

All non-specified quantitative parameters above are not item specifications and are provided only as general background; consult the CoA/Spec Sheet for the definitive item data.

Quality and Grades

• Item-specific grade/purity: Not specified for this item; refer to CoA/Spec Sheet.

• Interpreting quality for nucleic acid–small molecule conjugates (general information):

  • Purity metrics: For aptamer conjugates, purity may be reported by HPLC (e.g., analytical RP‑HPLC), LC–MS, and UV–Vis. Oligonucleotide integrity is commonly verified by LC–MS deconvolution and/or gel electrophoresis (literature). The small-molecule load and linker integrity are often confirmed by MS.
  • Identity confirmation: Mass accuracy within expected tolerance, correct isotopic pattern, and, where applicable, sequence confirmation by enzymatic digestion mapping.
  • Residual solvents/salts: Lyophilized materials can contain counterions (e.g., Na+, K+, NH4+). Reporting of residual salts, water, or solvent is product- and method-dependent.
  • Endotoxin/bioburden: For purely chemical research reagents not intended for biological administration, endotoxin testing is not typically required unless specified by the user application.

• Stabilizers and formulation:

  • If supplied in aqueous buffer, stabilizers (e.g., low salt, pH ~7–8) may be chosen to preserve aptamer structure and conjugate linkage. Any such excipients or stabilizers are not specified for this item; refer to CoA/Spec Sheet.

• Choosing fit-for-purpose grade (guidance):

  • For cell-based chemical biology, researchers typically require HPLC‑verified purity and LC–MS confirmation. For in vivo preclinical studies, additional specifications (sterility, endotoxin, sequence verification) may be sought, but are outside the scope of this catalog listing unless explicitly provided.

Reaction and Applications

• Manufacturer applications: Not specified beyond the catalog categorization; no explicit application text provided for this item.

• General/literature context for AS1411–VH032 type constructs (not product-specific claims):

  • Chemical biology probes: Aptamer–E3 ligase ligand conjugates have been investigated as targeted recruiters for proximity-induced protein modulation (e.g., degrader-like mechanisms) in research settings.
  • Targeting motif: AS1411 is a well-studied DNA aptamer reported to bind nucleolin (literature). Coupling to VH032 (a VHL ligand) is commonly used to engage the VHL E3 ligase complex.
  • Linker engineering: A C4 spacer typically balances flexibility and distance; researchers often vary linker length/chemistry to tune activity, permeability, and selectivity.
  • Assay types: Cell-based uptake/target engagement studies, fluorescence/imaging when a label is present, pull-down or proximity assays to explore ternary complex formation (literature).

• Practical tips (general):

  • Use nuclease‑free buffers, maintain consistent ionic strength/pH to preserve aptamer folding.
  • For cellular studies, prepare concentrated aqueous stocks (with minimal DMSO if required), filter through 0.22 µm when compatible, and perform serial dilutions immediately before use.
  • Include appropriate controls: unconjugated AS1411, scrambled aptamer controls, VH032 alone, and non-binding analogs to dissect mechanism (literature practice).

The above application discussion is general chemical biology guidance and not a guarantee of performance for this specific catalog item.

Reaction Conditions

This section is not typically applicable to a finished aptamer–small molecule conjugate supplied for research use, as it is not employed as a reagent in chemical transformations.

General literature context (not product-specific):

• Conjugation chemistries used to assemble similar materials are often conducted in aqueous/DMF or aqueous/DMSO co-solvent systems at pH 7.5–8.5 for amide couplings, or at room temperature for CuAAC with careful copper control to prevent oligo damage. Reaction times range from 1–16 h depending on coupling efficiency. Purification commonly uses RP‑HPLC with water/MeCN gradients containing volatile acids (e.g., 0.1% TFA or formic acid).

For this catalog item, no reaction conditions are provided or applicable; refer to the CoA/Spec Sheet for handling rather than synthetic use.

Safety and Handling

• Regulatory/SDS:

  • GHS classification: Not specified for this item; refer to SDS.
  • Signal word, hazard (H) statements, pictograms: Not specified for this item; refer to SDS.

• General laboratory precautions (non-item-specific best practice):

  • Handle in a clean area using good microbiological practice for nucleic acids to avoid nuclease contamination (use RNase/DNase-free plastics and reagents).
  • Wear appropriate PPE: lab coat, safety glasses, and nitrile gloves. Avoid inhalation of powders/aerosols and contact with skin/eyes.
  • Use a chemical fume hood when preparing concentrated DMSO stocks or when handling volatile reagents used with the product.

• Incompatibilities and stability (general guidance):

  • Avoid strong oxidants, strong acids/bases, and elevated temperatures that can accelerate oligonucleotide depurination or amide hydrolysis.
  • Protect from nucleases; use nuclease-free water/buffers and dedicated tools to limit cross-contamination.
  • Minimize repeated freeze–thaw cycles; aliquot upon first thaw.

• First-aid overview (consult SDS for authoritative instructions):

  • Eye/skin contact: Rinse with water for several minutes. Remove contaminated clothing.
  • Inhalation of dust: Move to fresh air; seek medical attention if symptoms persist.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical advice.

This product is for research use only. Always consult the current SDS and institutional EHS guidance for definitive safety and handling requirements.

Solvent Selection

• Item-specific solvent recommendations: Not specified for this item; refer to CoA/Spec Sheet.

• General guidance for aptamer–ligand conjugates (literature-based, not a product spec):

  • Primary: Nuclease‑free water, PBS (pH 7.2–7.4), or HEPES buffer (pH 7.4) are common vehicles owing to the hydrophilicity of oligonucleotide backbones.
  • Cosolvents: To aid dissolution of hydrophobic payloads, pre-wet with minimal DMSO (e.g., 1–5% v/v final) before dilution into aqueous buffer; verify compatibility with your biological assay.
  • Ionic considerations: Monovalent cations (K+, Na+) can modulate G‑quadruplex folding of AS1411 (literature). If target conformation is important, maintain consistent salt conditions when preparing stocks.

• Polarity/miscibility (general):

  • Aqueous buffers are fully miscible with small percentages of DMSO; avoid strong organic solvents (e.g., neat MeCN, DMF) for routine biological use as these can perturb aptamer folding or cell viability.

• When to choose alternatives:

  • For applications requiring stringent control of folding, use defined buffers (e.g., 10 mM KCl + 100 mM K+ salt background) to stabilize G‑quadruplex states (literature).
  • For purely chemical conjugation or analytical characterization, mixtures such as water/MeCN or water/MeOH with volatile buffers (e.g., TEA, HFIP for LC–MS) may be employed, ensuring the conjugate’s stability.

Always confirm solubility and stability empirically at small scale; the above are general recommendations and not item specifications.

Storage and Reconstitution

• Item-specific storage and shipping:

  • Storage Conditions: Store at −20°C (per product data).
  • Shipped In: Ice chest + ice pads (per product data).

• Item-specific reconstitution: Not specified for this item; refer to CoA/Spec Sheet.

• General guidance (literature-based, not a specification):

  • Upon receipt, keep frozen. If lyophilized, allow the vial to equilibrate to room temperature in a desiccator before opening to minimize moisture uptake.
  • Reconstitute with nuclease‑free water or buffer (e.g., PBS or HEPES, pH ~7.2–7.5) to prepare a concentrated stock. If needed, pre-wet with minimal DMSO to aid dissolution of hydrophobic moieties, then dilute into buffer.
  • Aliquot into low‑bind, nuclease‑free tubes to avoid multiple freeze–thaw cycles; store working aliquots at −20°C or below. For extended storage, −80°C is often preferred for nucleic acid conjugates.
  • Avoid repeated thawing; thaw on ice, mix gently (no vortexing if foaming/denaturation is a concern), and briefly spin down before use.
  • Protect from light if the construct contains chromophores; use amber vials when appropriate.

Always defer to the product’s CoA/Spec Sheet for any item-specific instructions or composition information.

Structure and Identity

• 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.

• Nomenclature and inferred construct (general/literature context, not a product specification):

  • The name “AS1411-C4-VH032” suggests a conjugate in which the nucleolin-binding DNA aptamer AS1411 is linked via a 4‑carbon spacer (C4) to the VHL E3 ligase ligand VH032. Such constructs are reported in the chemical biology literature as targeted delivery/degrader chimeras (e.g., aptamer–ligand bioconjugates).

• Structural features (general, descriptive):

  • AS1411 is a guanine-rich oligonucleotide aptamer known to form G‑quadruplex motifs (literature). If present, these secondary structures impart high negative charge density (phosphate backbone) and potential cation (K+/Na+) sensitivity.
  • VH032 is a hydroxyproline-based small-molecule ligand for the von Hippel–Lindau (VHL) E3 ligase (literature). It typically bears multiple hydrogen-bond donors/acceptors and amide linkages.
  • A “C4” linker typically indicates a butylene tether between the two components, potentially through amide/ether linkages depending on the chosen conjugation chemistry (literature).

• 2D structural description (general, not item-specific):

  • One domain is a polyanionic oligonucleotide strand (AS1411) capable of G‑quadruplex topology; the other is a compact VH032 scaffold with amide-rich functionality. The two are connected by an alkyl spacer (≈ four methylenes), often via an amide or click-compatible handle. Exact sequence, stereochemistry, and connection sites are not specified for this item; refer to CoA/Spec Sheet.

Synthetic Utility

• Role in synthesis:

  • This product is a specialized conjugate intended as a chemical biology probe rather than a common synthetic building block or reagent. It is not typically used as a solvent, coupling partner, or catalyst.

• General synthetic insights (literature-based, not item-specific):

  • Construction of aptamer–ligand conjugates commonly employs: (i) amide coupling between a functionalized ligand (e.g., VH032‑COOH) and an amino-modified oligonucleotide; (ii) click chemistry (CuAAC/SPAAC) using azide/alkyne handles; or (iii) NHS‑ester coupling to amine-terminated linkers.
  • Linker selection (e.g., C4 alkyl spacers) modulates spatial reach and flexibility; shorter linkers can enhance rigidity but may reduce productive ternary complex formation, whereas longer linkers can increase entropic cost.
  • Purification is typically achieved by RP‑HPLC or ion‑exchange HPLC; identity confirmed by LC–MS. Protecting group strategies and orthogonal handles are key to maintaining oligonucleotide integrity during conjugation.

• Retrosynthetic perspective:

  • Break the conjugate into three modules: (1) AS1411 aptamer (sequence-defined oligomer with terminal functional handle), (2) linker unit (C4 spacer with orthogonal termini), (3) VH032 derivative bearing a conjugation-ready function. Reassemble via chemoselective ligations under aqueous-compatible conditions.

These points are general to the class and not specific to this item’s manufacturing route or specifications.

Target Specificity

• Target, epitope, species reactivity, clone/isotype: Not specified for this item; refer to CoA/Spec Sheet.

Note: Although AS1411 is widely discussed in the literature for binding nucleolin, no target specificity is stated for this specific catalog item. Users should consult the product documentation and perform appropriate controls to confirm target engagement in their system.