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| Targets |
Propargyl-PEG1-SS-PEG1-acid does not have a specific biological target, as it is a chemical linker. Its function is to serve as a covalent connector between two or more molecular components. The "targets" of this linker are the specific functional groups on the molecules it is designed to conjugate. The carboxylic acid group is a target for conjugation with molecules that contain primary amines, forming a stable amide bond. The propargyl group is a target for click chemistry, reacting specifically with azide groups to form a 1,2,3-triazole linkage. The disulfide bond is a target for reduction in the intracellular environment, specifically by the high concentrations of glutathione (GSH) found inside cells. This reductive cleavage is the mechanism by which the linker releases its payload. Therefore, the biological "target" is the intracellular environment of the target cell, where the high GSH concentration triggers the cleavage of the disulfide bond. The PEG spacer does not have a biological target but serves to link the functional groups and improve the overall properties of the conjugate. In the context of ADC design, the linker's role is to ensure that the potent cytotoxic drug is stably attached to the antibody in circulation but is efficiently released once the ADC is internalized by the cancer cell.
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| ln Vitro |
ADC cytotoxins are connected to antibodies through an ADC connector to form ADCs [1].
As a chemical linker, Propargyl-PEG1-SS-PEG1-acid does not possess any direct in vitro biological activity. Its biological relevance is entirely indirect, stemming from its use in the synthesis of bioactive conjugates. The in vitro activity of this linker is assessed through the characterization of the final conjugates it helps to create. For instance, when used to synthesize an ADC, the activity of the conjugate is evaluated in cell-based assays for target binding, internalization, and cytotoxicity. The cleavable disulfide bond contributes to the conjugate's overall activity by ensuring the efficient release of the toxic payload inside the target cell, which is a critical factor for the ADC's potency. In a typical in vitro experiment, the ADC is incubated with cancer cells, and cell viability is measured. The potency of the ADC depends on the linker's ability to be cleaved intracellularly, releasing the active drug. The performance of the linker can be assessed by comparing the activity of an ADC made with this cleavable linker to one made with a non-cleavable linker. Thus, the "activity" of Propargyl-PEG1-SS-PEG1-acid is a measure of its ability to function as a cleavable bridge that enables the targeted delivery of a therapeutic payload. |
| ln Vivo |
As a chemical linker, Propargyl-PEG1-SS-PEG1-acid does not possess any direct in vivo biological activity. It is not administered as a therapeutic agent and does not exert pharmacological effects in animal models. Its in vivo relevance is strictly as a component of larger, biologically active conjugates. When incorporated into an ADC, the cleavable disulfide linker plays a critical role in the drug's in vivo efficacy. The linker must be stable in the bloodstream (where glutathione concentrations are low) to prevent premature release of the toxic payload and systemic toxicity. However, once the ADC is internalized into the target cell, the high concentration of glutathione in the cytoplasm reduces the disulfide bond, releasing the active drug. This targeted release mechanism is known as the "bystander effect" and is a key design consideration for ADCs. The specific in vivo activity—such as tumor regression—is determined by the conjugate's warhead and targeting ligand, but the linker's stability and cleavage kinetics are essential for the overall therapeutic outcome. Therefore, while Propargyl-PEG1-SS-PEG1-acid has no direct in vivo activity, it is a critical component that influences the efficacy and safety of the therapeutics it is used to construct.
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| Enzyme Assay |
There are no specific in vitro enzyme or receptor binding assays for Propargyl-PEG1-SS-PEG1-acid, as it is not a biologically active compound. Its characterization is performed using analytical chemistry techniques such as NMR, HPLC, and MS to verify its structure and purity. To confirm its functionality, chemical assays are used. The reactivity of the carboxylic acid group can be tested by reacting it with an amine-containing compound and monitoring the formation of the amide bond. The reactivity of the propargyl group can be tested in a click chemistry reaction with an azide-containing fluorophore, and the successful conjugation can be confirmed by HPLC or LC-MS. The cleavability of the disulfide bond can be tested in vitro by incubating the linker or a model conjugate with a reducing agent such as dithiothreitol (DTT) or glutathione, and monitoring the cleavage products by HPLC. These are quality control and functional validation steps to ensure the linker is active and can be used for its intended purpose. There are no biological assays for this compound.
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| Cell Assay |
There are no standard in vitro cell-based assays for Propargyl-PEG1-SS-PEG1-acid, as it is not a bioactive molecule. Its use in cell biology is indirect, as a reagent for constructing ADCs. In such cases, the cell-based assay would involve treating cells with the final ADC and then measuring a biological readout, such as cell viability. The performance of the linker would be evaluated by the potency and selectivity of the ADC, which depend on the linker's ability to release the payload inside the cell. For example, a common assay is to treat cancer cells with varying concentrations of the ADC and measure cell viability after 72 hours using an MTT or CellTiter-Glo assay. The IC50 of the ADC is then calculated. To confirm that the activity is dependent on the cleavable linker, a control ADC with a non-cleavable linker can be used. However, there is no direct assay for the linker itself in cells, as it is not designed to interact with cells in its unconjugated form. Any cell-based work involving this linker is always part of a larger experimental design to evaluate a specific therapeutic conjugate.
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| Animal Protocol |
Propargyl-PEG1-SS-PEG1-acid is not used in in vivo animal experiments as a standalone compound. It is a synthetic building block for creating ADCs and other bioconjugates. Animal studies involving this compound would only be conducted on the final, larger conjugates that incorporate it. In such studies, the linker's contribution to the overall pharmacokinetic and pharmacodynamic profile of the conjugate would be assessed. For example, researchers might compare the in vivo efficacy, stability, and toxicity of an ADC synthesized with this cleavable disulfide linker to an ADC synthesized with a non-cleavable linker. The cleavable linker is expected to release the toxic payload inside the tumor, leading to better efficacy and a wider therapeutic index. However, there is no standard animal protocol for the linker itself. Its use is limited to the research and development phase, where it is employed in the chemical synthesis of test articles. The storage recommendations (e.g., 2-8°C) are for maintaining the chemical integrity of the reagent. In summary, there are no in vivo animal experiments for this linker as a single agent.
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| ADME/Pharmacokinetics |
The pharmacokinetic (PK) properties of Propargyl-PEG1-SS-PEG1-acid are not studied as it is not a therapeutic agent. However, its physicochemical properties provide insight into its behavior. It has a molecular weight of 264.36 g/mol and a molecular formula of C10H16O4S2. It is a relatively small molecule with a predicted boiling point of 428.8°C and a density of 1.243 g/cm³. It is soluble in water, DMSO, DCM, and DMF, indicating good versatility for various applications. It has a pKa of 4.27, which is typical for a carboxylic acid. For storage, it is recommended to keep it at 2-8°C. As a small, hydrophilic molecule, it would be expected to have a short half-life if introduced into the bloodstream, likely being rapidly cleared by renal filtration. However, when conjugated to larger molecules like antibodies, the overall PK is dominated by the larger component. The "PK" properties of this linker are thus not an independent consideration but are integral to the design and performance of the bioconjugates it helps to create, particularly its cleavable disulfide bond which is designed to release the payload specifically in the target tissue.
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| Toxicity/Toxicokinetics |
As a PEG-based linker, Propargyl-PEG1-SS-PEG1-acid is considered to have low toxicity. PEG polymers are widely regarded as biocompatible and non-toxic. The compound is classified as a research reagent, and standard laboratory safety precautions should be followed when handling it. The safety of this linker is primarily considered in the context of its use in ADCs. A cleavable linker is designed to be stable in circulation but to release its payload inside the target cell. If the disulfide bond were to be reduced prematurely (e.g., in the bloodstream), it could lead to the release of the toxic payload into the bloodstream, causing off-target toxicity. Therefore, the toxicity of the linker itself is not the primary concern, but rather the toxicity of the payload it is designed to carry if the linker fails to perform its function correctly. Its toxicity profile has not been extensively studied independently, but due to its intended use and chemical class, it is not expected to be acutely toxic. All handling should be done with appropriate personal protective equipment (PPE) in a well-ventilated area.
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| References |
[1]. Beck A, et al. Strategies and challenges for the next generation of antibody-drug conjugates. Nat Rev Drug Discov. 2017 May;16(5):315-337.
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| Additional Infomation |
Propargyl-PEG1-SS-PEG1-acid is a research-use-only reagent and is not a drug, nor is it approved for any clinical or therapeutic use. It is a highly versatile chemical tool with key applications in the synthesis of antibody-drug conjugates (ADCs). Its structure features a disulfide bond that makes it a cleavable linker, a propargyl group for click chemistry, and a carboxylic acid for amide bond formation. This combination of functionalities makes it an ideal linker for creating ADCs with controlled intracellular drug release. The disulfide bond is cleaved by the high concentration of glutathione in the intracellular environment, ensuring that the cytotoxic payload is released specifically inside the target cancer cell. The alkyne group enables copper-catalyzed azide-alkyne cycloaddition (CuAAc) with azide-containing molecules, providing a versatile method for further functionalization. The short PEG spacer improves solubility and flexibility while maintaining a compact structure. This linker is therefore an essential tool for medicinal chemists and chemical biologists working on targeted drug delivery and bioconjugation.
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| Molecular Formula |
C10H16O4S2
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| Molecular Weight |
264.361640930176
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| Exact Mass |
264.049
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| CAS # |
1807503-85-0
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| PubChem CID |
91757789
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| Appearance |
Light yellow to yellow viscous liquid
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
428.8±45.0 °C at 760 mmHg
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| Flash Point |
213.1±28.7 °C
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| Vapour Pressure |
0.0±2.2 mmHg at 25°C
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| Index of Refraction |
1.545
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| LogP |
2.15
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
16
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| Complexity |
224
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(CCOCCC(=O)O)SCCOCC#C
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| InChi Key |
OEMFYMUYWYWVRT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C10H16O4S2/c1-2-4-13-6-8-15-16-9-7-14-5-3-10(11)12/h1H,3-9H2,(H,11,12)
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| Chemical Name |
3-[2-(2-prop-2-ynoxyethyldisulfanyl)ethoxy]propanoic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.7827 mL | 18.9136 mL | 37.8272 mL | |
| 5 mM | 0.7565 mL | 3.7827 mL | 7.5654 mL | |
| 10 mM | 0.3783 mL | 1.8914 mL | 3.7827 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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