PEG Silane Reagents (for glass or silicone surface modification)

Ethoxy or methoxyl silane functionalized polyethylene glycol, Silane PEG (PEG-Si) is a surface reactive PEG derivative that can be used to modify glass, silica, silicone and other surfaces via the reaction between hydroxyl group and triethoxyl silane.  They can thus functionalize these support with groups that will confer other physico-chemical properties, such a amine, COOH, or SH, Maleimide, succinimidyl (NHS), and Biotin.  Hence, pegylation can greatly suppress the non-specific binding of charged molecules to the modified surfaces.  And they have wide applications for medical devices, biomedical/ biological microelectromechanical systems and biocompatible material development. Other applications include special optical lenses, purification…

What’s the difference between monodisperse and polydisperse PEG?

Polyethylene glycol (PEG) is a synthetic, hydrophilic, biocompatible polymer with widespread use in biomedical and other applications. It is non-toxic, FDA-approved, usually nonimmunogenic, and is often used in many biomedical applications including bioconjugation, drug delivery,  surface functionalization, and tissue engineering. Bioconjugation with PEG (also called PEGylation) is the covalent conjugation of drug targets such as peptides, proteins, or oligonucleotides with PEG which can effectively improve their water-solubility and circulation half-life of medicines, resulting in enhanced safety and therapy effects .  In drug delivery, PEGs can be used as linkers for antibody-drug conjugates (ADCs) or as a surface coating on nanoparticles to improve systemic drug delivery.

What’s the difference between monodisperse and polydisperse PEG?​

At present, most of the polyethylene glycol compounds supplied on the market are polymers formed by the polymerization of ethylene glycol. The molecular weight of polydisperse PEG is uncertain, and distributed in a certain range. Often polydispersity index (PDI) is used to determine how narrow the molecular weight distribution is. On the country,Monodisperse PEG refers to a polyethylene glycol (PEG) with a precise, discrete molecular weight (ie, with a fixed molecular weight rather than a range).

According to some researches, the use of polydisperse PEG linkers in drug development has led to problems in biological applications due to steric hindrance and binding. Thus, monodispersed PEG linkers have become more commercially viable now, which has been found to be beneficial in drug design, specifically in small molecule drugs. The introduction of monodispersed PEG linkers to small molecule drugs increases the drug’s solubility and molecular weight, which extend drug half-life in the body.

One of Biochempeg‘s goals in manufacturing PEG linkers is to ensure high quality products for worldwide clients. We aim to manufacture monodisperse PEG linkers with high purity and a single molecular weight.

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FDA Approved PEGylated Drugs 2019

What is PEGylateion? What are the PEGylated drugs used for? PEGylation is the process of the strands attachment of the polymer PEG to molecules and macrostructures, such as a drug, therapeutic protein or vesicle, that can improve the safety and efficiency of many therapeutics. The chain binds to the drugs covalently and build it sterically stable. Thus, the PEGylated proteins or peptides are non-toxic, non-antigenic, non-immunogenic, and highly water soluble. In addition, it further increases half-life of the PEGylated drugs and reduces dose frequency by preventing renal excretion of drugs.

PEGylation products consists of various reagents including linkerscross-linkers, and labels. Different reagents include AMINE, CARBOXYL, and CARBOXYL PEGylation. The PEGylated drugs currently are used in the treatment of cancer, chronic kidney diseases, hepatitis, multiple sclerosis, hemophilia, and gastrointestinal disorders.  ADAGEN manufactured by Enzon Pharmaceuticals, Inc., US was the first PEGylated protein approved by the U.S. Food and Drug Administration (FDA) in March 1990, to enter the market. Since the introduction of ADAGEN, a mass of PEGylated protein and peptide drugs have kept up the footsteps and many others are under clinical trial or under development stages. Among the FDA approved drugs, Pegasys and Neulasta, exceeded $5 billion in 2011. It’s worth mentioning that all of the FDA approved drugs containmethoxypoly (ethylene glycol) or mPEG. Below, we lists all of the FDA Approved PEGylated Drugs on the market.

fda-approved-pegylated-drugs

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About Polymer PEG and Monodisperse PEG

Polymer PEG Derivatives has been used in medicine, materials, chemical and other fields.

At present, most of the polyethylene glycol compounds supplied on the market are polymers formed by the polymerization of ethylene glycol. The molecular weight of polymer PEG compounds is uncertain, and distributed in a certain range. It will be difficult to quantify the modified compounds in practice because of  disperse molecular weight. In addition, it is very difficult to separate and purify polyethylene glycol compounds because of their similar structure, so it is particularly important to design a synthesis method of monodisperse polyethylene glycol(PEG) derivatives.
Monodisperse polyethylene glycol(PEG) molecular weight is fixed. It can not be obtained by polymerization. It must be by the appropriate reaction of the basic polyethylene glycol fragment.
At present, the monodisperse custom synthesis PEG is difficult, the literature is less reported and poor, and the price of monodisperse polyethylene glycol sold on the market is also expensive. For the above reasons, an economical and efficient monodisperse polyethylene glycol synthesis method need to be designed, which can provide with higher quality and lower price.

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Overviews of the Antibody-drug conjugates (ADCs)

Antibody-drug conjugates (ADCs) consist of a desirable monoclonal antibody, an active drug and an appropriate linker. An appropriate linker between the antibody and the drug maintain ADCs’ stability and provides a specific bridge, and thus helps the antibody to selectively deliver the drug to tumor cells and accurately releases the drug at tumor sites.
The selection of ADC PEG linker is target dependent, based on the knowledge of the used active drugs including cytotoxin, the internalization and degradation of the antibody-target antigen complex, and a preclinical in vitroand in vivo activity comparison of conjugates.
Monodisperse poly(ethylene glycols) PEGs is one kind of most widely used linker in targeted therapy. With many features, such as high-usage rate,targeting, regulate PH value etc. With multitudinous choice of functional groups, PEG linkers can conjugates with different antibodies and drugs , then forming different linker, such as pH-sensitive Linker, Disulfide Linker, β-Glucuronide Linker… 
Monodisperse Amine-PEG-carboxy l work as small molecular linkers, content hydrophilic groups and can solute in most solvents, for this case Amine group also widely use in ADC design. More over, Amine group linked with matched antibody or drug can worked as pH-sensitive Linker.

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Anticancer drug carrier

Biodegradable multi-blocked polyurethane (PU) based micelles with a hydrophilic PEG corona were extensively studied for anti-cancer drug delivery systems. The hydrophilic PEG segment usually incorporated as a soft segment or as an end capping reagent, which has difficulty forming a dense PEG coating with a brush like conformation due to the low mobility of the Polymer PEG Derivatives domains at the soft segment and the low amount of the PEG at the end of PU chains. In the present study, biodegradable pH sensitive polyurethane micelles with a dense brush like coating of PEG were prepared by a new kind of PEG grafted polyurethanes (PEG-g-PU) which were synthesized using PEGylated diethanolamine (MPEG-DEAM) as a chain extender. The high mobility of pendant MPEG in PEG-g-PU results in the formation of a dense and brush like PEG corona on the PEG-g-PU micelles. Meanwhile the MPEG attached on the hard segment will transfer the diethanolamine (DEAM) to the surface of nanoparticles during the self-assembly process and the DEAM render the particles with positive charges which potentially enhances cellular uptake and endosomal escape. DLS, TEM and AFM showed that a dense PEG domain was formed on the surface of PEG-g-PU micelles while no obvious PEG microdomain was observed for the other two kinds of micelles. FTIR and DSC results demonstrated the enhanced microphase separation of PEG-g-PU micelles compared with PEG-g-PU bulk materials and the other two contrast PU micelles, i.e. PEG-b-PU and PEG-c-PU. Paclitaxel (PTX) was chosen as a model hydrophobic drug to evaluate the loading and pH-triggered release of the PU micelles. The enhanced cytotoxicity of PTX-loaded PEG-g-PU-3 micelles against H460 cancer cells reveals that they are more potent for intracellular delivery of PTX as compared to PEG-b-PU-3 and PEG-c-PU-3 micelles.

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About PEGylation products

However, we have now collected a number of dozens of revealed papers that describe the usage of our products with experimental details. However, a low molecular weight monodisperse PEG similar to PEG 400, supplies approximately 30% less response in comparison with its greater molecular weight counterparts. Our merchandise are in dry powder type besides these having very low molecular weight. For long term storage, we advocate that our products are saved as a dry powder form and never in any type of options. Emulsifying brokers are soluble in fat and water to allow uniform dispersion of fat in water. Natural emulsifying brokers are derived from plant and animal tissues and largely within the form of hydrated lypophilic colloids. Shea, Cocoa, Mango, Olive, and Avocado Butter are all excellent bases for a moisturizer. A: All of our merchandise are shipped at room temperature for overnight supply within the US. Before vials will be opened, please enable vials and merchandise to equilibrate to room temperature to keep away from absorbing moisture.

A: Our merchandise could be sensitive to temperature, gentle or moisture. Q: What PEG merchandise are significantly sensitive to light or oxygen? Also the natural emulsifiers need preservatives as these are subjected to microbial progress. These products embrace PEGylated enzymes, monoclonal antibodies, glycoproteins, cytokines, human growth hormones, aptamers, artificial peptides, and liposomes. A: There are at the moment about one dozen of PEGylated pharmaceuticals available on the market with FDA approval. Dr. Sherman’s data suggests that using the methoxy-terminated PEG may enhance the risk of forming antibodies to PEG, which is able to in turn hasten the accelerated blood clearance (ABC) phenomenon seen with some PEGylated medicine. Vinyl sulfone PEG, phospholipid PEG and IR dye PEG derivatives obtainable.  Alfa Chemistry offers a wide range of PEG linkers that enhance drug solubility and stability, and discover new drug supply formats.

A: We provide quite a lot of PEG acid and NHS ester PEG. Type A: SCMMethylene (CH2) linkage between PEG and NHS ester PEG Highly reactiveHydrolysis half-life: less than five minutes. Type B: SGC4 aliphatic ester linkage between PEG and NHS esterVery reactiveHydrolysis half-life: round 20 minutes. Type C: SS C3 aliphatic ester linkage between PEG and NHS esterVery reactiveHydrolysis half-life: round 10 minutes. These NHS esters react with major and secondary amine to type a stable amide linkage. To PEGylate proteins or nanoparticles, it typically requires a big excess of PEG NHS esters as a result of competitive hydrolysis reaction in an aqueous resolution. Stability of NHS esters is compared by their hydrolysis half-life (T1/2). Q: What are the variations among PEG NHS ester merchandise? PEG carboxyl acid can be used to react with amine groups with peptide coupling reagents reminiscent of NHS. Such applications include peptide synthesis, section switch catalysis, pharmaceutical modification, protein and cell purifications, polymer-certain reagents, and binding assays.

Q: What are the storage situations in merchandise?

A: PEGylation products are very soluble in water and aqueous buffer options typically with solubility as much as a number of hundred milligrams per milliliter (mg/mL). As an example, 1.Zero MOL % labeling implies that certainly one of every one hundred monomeric units alongside the polysaccharide chain is fluorescently labeled. Q: What’s the definition for Labeling Degree (%) of your fluorescently-labeled polysaccharide products? Usually the molecular weight (MW) of multi-arm PEG merchandise refers to the molecular weight of the complete molecule, and the molecule weight of every arm might be calculated by dividing the indicated MW by the indicated number of arms.

PEG-DSPE block copolymers and their derivatives as nanomaterials in drug delivery

Poly(ethylene glycol)–distearoylphosphatidylethanolamine (DSPE-PEG) block copolymers are biocompatible and amphiphilic polymers that can be widely utilized in the preparation of liposomes, polymeric nanoparticles, polymer hybrid nanoparticles, solid lipid nanoparticles, lipid–polymer hybrid nanoparticles, and microemulsions. Particularly, the terminal groups of PEG can be activated and linked to various targeting ligands, which can prolong the circulation time, improve the drug bioavailability, reduce undesirable side effects, and especially target specific cells, tissues, and even the intracellular localization in organelles.

Poly(ethylene glycol)–distearoylphosphatidylethanolamine (PEG-DSPE) block copolymers are amphiphilic, have been approved by the Food and Drug Administration for medical applications, and have been widely used in the preparation of liposomes, polymeric nanoparticles, polymer hybrid nanoparticles, and solid lipid nanoparticles, among others. The amphiphilic polymers are nanostructures composed by a hydrophobic core (DSPE) and a hydrophilic shell (PEG). The core–shell structure can encapsulate and carry poorly water-soluble drugs to congregate in the core of DSPE, and the PEG shell reduces the in vivo clearance of cholesterol-free liposomal formulations and the adsorption of plasma proteins. Therefore, utilizing PEG-DSPE for the formation of nanostructures could prolong the body circulation time and release drugs at a sustained rate in an optimal range of drug concentrations. Molecular therapy, including gene therapy, is a promising strategy for the treatment of human diseases. However, delivery of molecular therapeutics efficiently and specifically to the targeted tissue remains a significant challenge.

Carboxyl-terminated PEG-DSPE

Carboxyl groups are introduced to the terminal groups of DSPE-PEG block copolymers, which can easily react with the ligands for active target cells or tissues, such as transferring and peptide.9–11 Several reports have successfully synthesized DSPE-PEG-COOH.12–14 In brief, DSPE in chloroform methanol was added to PEG-bis(succinimidyl succinate) (PEG-2OSu) in chloroform, followed by the addition of triethylamine. The reaction mixture was stirred vigorously overnight at room temperature. Full conversion of the primary amino group of DSPE was confirmed by the negative ninhydrin reactivity after separating the products by thin-layer chromatography.

Amino-terminated PEG-DSPE (amino-PEG-DSPE)

The amino group of the heterobifunctional PEG is selectively protected by such protective groups as fluorenylmethyloxycarbonyl and butyloxycarbonyl (Boc). The other end of PEG is the active group that reacts with DSPE. The protective groups are then removed after the reaction to form amino-PEG-DSPE. Also, amino-PEG-DSPE can be combined with small-molecule medicines and ligands.

PEGylated liposomes have attracted considerable attention as the passive targeting administration carriers for the therapy of cancer and infectious diseases. They outweigh other carriers in increasing the systemic circulation time of drugs, delivering active molecules to the site of action and preventing damage of healthy tissue from toxic effects. During the preparation, the key step of developing long-circulating liposomes was accompanied by the inclusion of the synthetic polymer PEG in the liposome composition, such as PEG-DSPE. The incorporation of PEG-DSPE in the lipid-based carriers substantially prolongs the circulation lifetime of the liposomes.  PEG-DSPE would significantly increase the plasma circulation longevity of the liposomes from 1,2-distearoyl-sn-glycero-3-phosphatidylcholine (DSPC). The aggregation of DSPC-based liposomes was completely precluded with PEG-DSPE suggesting that PEG-DSPE, 2000 reduced the in vivo clearance of cholesterol-free liposomal formulations and the adsorption of plasma proteins primarily by inhibiting surface interactions and particularly by liposome-liposome aggregation.

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Perfect upgrade on quality,new breakthroughs in Click Chemistry Series Product

1. A heterobifunctional peg bioorthogonal linker with azide (click reaction) and amine reactivity
The advent of bioorthogonal chemical biology tools for imaging and tracking of biomolecules (proteins, lipids, glycans) in their native environment is providing unique insights into cellular processes that are not achievable with traditional biochemical or molecular biology tools. However, the use of copper in traditional click labeling chemistry limits its application in chemistry biology research wherein oligonucleotide or polysaccharide involved could be degraded by copper. The advancement of metal-free bioorthogonal cycloaddtions between strain-promoted alkyne, so called cyclooctynes, with azide (SPAAC), tetrazines or nitrones (SPANC) could solve this issue. Among the cyclooctyned invented, bicyclo[6.1.0]nonyne (BCN) featuring Cs symmetry displays excellent cycloaddition reaction kinetics.

Biocompatible – click reaction occurs efficiently under mild buffer conditions; requires no accessory reagents such as a copper catalyst or reducing agents (e.g. DTT)

Chemoselective – azides and BCN groups do not react or interfere with other functional groups found in biological samples but conjugate to one another with high efficiency.

Amine reactivity – modify amine-containing molecules or biomolecules with BCN moiety for subsequent conjugation/labelling with azide counterpart.

2. Copper-free click click reagents is a bioorthogonal reaction developed as an activated variant of an azide alkyne Huisgen cycloaddition. Cu-free click chemistry has been modified to be bioorthogonal by eliminating a cytotoxic copper catalyst, allowing reaction to proceed quickly and without live cell toxicity. Although the reaction produces a regioisomeric mixture of triazoles, the lack of regioselectivity in the reaction is not a major concern for its applications in bioorthogonal chemistry. More regiospecific and less bioorthogonal requirements are best served by the traditional Huisgen cycloaddition, especially given the low yield and synthetic difficulty (compared to the addition of a terminal alkyne) of synthesizing a strained cyclooctyne. The incredible bioorthogonality of the reaction has allowed the Cu-free click reaction to be applied within cultured cells, live zebrafish, and mice.

Dibenzylcyclooctyne (DBCO) is widely used in the Cu-free click chemistry. DBCO eliminates the use of cytotoxic copper catalyst, and allows reaction to proceed quickly and without live cell toxicity.
This acid functionalized cyclooctyne derivative is useful in strain-promoted copper-free azide-alkyne cycloaddition reactions. This dibenzocyclooctyne will react with azide functionalized compounds or biomolecules without the need for a Cu(I) catalyst to result in a stable triazole linkage.

Biocompatible – click reaction occurs efficiently under mild buffer conditions; requires no accessory reagents such as a copper catalyst or reducing agents (e.g. DTT)

Chemoselective – azides and DBCO groups do not react or interfere with other functional groups found in biological samples but conjugate to one another with high efficiency

Primary amine reactivity – modify amine-containing molecules with DBCO for use in advanced crosslinking experiments.

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PEG Hydrogels Applications in Drug Delivery and 3D Cell Culture

Applications of Polyethylene Glycol Hydrogels in Wound Healing and Tissue Regeneration

A major reported use of peg derivatives is for the development of hydrogels. Among the common uses of PEG hydrogels are the use as adhesives for wound closure, as controlled release matrices for therapeutics, for wound healing, as part of medical devices, and as regenerative medicine tools. A biodegradable cytocompatible bioadhesive hydrogel system from on oxidized methacrylated alginate/8-arm polyethylene glycol amine used for culture of human bone marrow-derived mesenchymal stem cells. The swelling behavior, degradation profiles, and storage moduli of the hydrogel bioadhesive were adjusted by varying the degree of oxidation of the alginate.

Applications of Polyethylene Glycol Hydrogels in Cell Culture and Tissue Models

PEG and PEG-copolymer hydrogels are practical solutions as scaffolds and have been used for cell culture; for controlled release of therapeutics; and for various other applications, including but not limited to tissue engineering. Larger amounts of ammonia cross linker used in the polymerization of an 8 arm PEG macromere, lead to higher crosslinking density and bulk of hydrogels, an increased surfaceelasticity and, generally, to smoother surface morphologies.

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