Name: m-PEG1-NHS ester
Brand: BOC Sciences
Rating: 5 (1 reviews)

Synonyms

2, 5-Dioxopyrrolidin-1-yl 3-methoxypropanoate

IUPAC Name

(2,5-dioxopyrrolidin-1-yl) 3-methoxypropanoate

Canonical SMILES

COCCC(=O)ON1C(=O)CCC1=O

InChI

InChI=1S/C8H11NO5/c1-13-5-4-8(12)14-9-6(10)2-3-7(9)11/h2-5H2,1H3

InChIKey

GDPPBYZKFKEXML-UHFFFAOYSA-N

Appearance

Solid powder

Shipping

Room temperature, or blue ice upon request.

Storage

Powder, -20°C, 3 years; In solvent, -80°C, 6 months; -20°C, 1 month

m-PEG1-NHS ester, a reactive polyethylene glycol derivative, is a versatile compound commonly found in bioconjugation and surface modification applications. Here are four key applications of m-PEG1-NHS ester:

Protein Modification: Widely utilized in protein PEGylation, m-PEG1-NHS ester plays a pivotal role in attaching polyethylene glycol chains to protein molecules. This modification not only boosts protein solubility and stability but also extends their circulating half-life, rendering them invaluable in therapeutic protein formulations. PEGylated proteins often exhibit reduced immunogenicity and improved pharmacokinetics, elevating their efficacy as pharmaceutical agents.

Surface Coating: Within the realm of biomaterials science, m-PEG1-NHS ester finds its niche in surface modification of medical devices and implants. By coating surfaces with PEG, it mitigates protein adsorption and cell adhesion, thereby minimizing immune responses and biofouling.

Drug Delivery Systems: Serving as a foundational component in liposome and nanoparticle design for drug delivery, m-PEG1-NHS ester stands at the forefront of innovation. Through the conjugation of PEG to drug carriers, it imparts a unique ‘stealth’ property that enables carriers to evade immune detection and prolong circulation time. This strategic approach significantly enhances the delivery and efficacy of encapsulated drugs to targeted tissues.

1.Antibodies against polyethylene glycol in healthy subjects and in patients treated with PEG-conjugated agents

Garay RP, El-Gewely R, Armstrong JK, Garratty G, Richette P.

In contrast to the accepted general assumption that polyethylene glycol (PEG) is non-immunogenic and non-antigenic, animal studies clearly showed that uricase, ovalbumin and some other PEGylated agents can elicit antibody formation against PEG (anti-PEG). In humans, anti-PEG may limit therapeutic efficacy and/or reduce tolerance of PEG-asparaginase (PEG-ASNase) in patients with acute lymphoblastic leukemia and of pegloticase in patients with chronic gout, but did not impair hyposensitization of allergic patients with mPEG-modified ragweed extract or honeybee venom or the response to PEG-IFN in patients with hepatitis C. Of major importance is the recent finding of a 22 - 25% occurrence of anti-PEG in healthy blood donors, compared with a very low 0.2% occurrence two decades earlier. This increase may be due to an improvement of the limit of detection of antibodies during the years and to greater exposure to PEG and PEG-containing compounds in cosmetics, pharmaceuticals and processed food products. These results raise obvious concerns regarding the efficacy of PEG-conjugated drugs for a subset of patients. To address these concerns, the immunogenicity and antigenicity of approved PEGylated compounds should be carefully examined in humans. With all these data in hand, patients should be pre-screened and monitored for anti-PEG prior to and throughout a course of treatment with a PEGylated compound. Finally, protein conjugates with the poorly immunogenic hydroxy-PEG sequence or other hydrophilic polymers are in early phases of development and may represent an alternative to immunogenic PEGylated proteins.

2.PEG-lipid micelles enable cholesterol efflux in Niemann-Pick Type C1 disease-based lysosomal storage disorder

Brown A, Patel S, Ward C, Lorenz A, Ortiz M, DuRoss A, Wieghardt F, Esch A, Otten EG, Heiser LM, Korolchuk VI, Sun C, Sarkar S, Sahay G.

2-Hydroxy-propyl-β-cyclodextrin (HPβCD), a cholesterol scavenger, is currently undergoing Phase 2b/3 clinical trial for treatment of Niemann Pick Type C-1 (NPC1), a fatal neurodegenerative disorder that stems from abnormal cholesterol accumulation in the endo/lysosomes. Unfortunately, the extremely high doses of HPβCD required to prevent progressive neurodegeneration exacerbates ototoxicity, pulmonary toxicity and autophagy-based cellular defects. We present unexpected evidence that a poly (ethylene glycol) (PEG)-lipid conjugate enables cholesterol clearance from endo/lysosomes of Npc1 mutant (Npc1(-/-)) cells. Herein, we show that distearyl-phosphatidylethanolamine-PEG (DSPE-PEG), which forms 12-nm micelles above the critical micelle concentration, accumulates heavily inside cholesterol-rich late endosomes in Npc1(-/-) cells. This potentially results in cholesterol solubilization and leakage from lysosomes. High-throughput screening revealed that DSPE-PEG, in combination with HPβCD, acts synergistically to efflux cholesterol without significantly aggravating autophagy defects. These well-known excipients can be used as admixtures to treat NPC1 disorder. Increasing PEG chain lengths from 350 Da-30 kDa in DSPE-PEG micelles, or increasing DSPE-PEG content in an array of liposomes packaged with HPβCD, improved cholesterol egress, while Pluronic block copolymers capable of micelle formation showed slight effects at high concentrations. We postulate that PEG-lipid based nanocarriers can serve as bioactive drug delivery systems for effective treatment of lysosomal storage disorders.

3.Selectivity of binding of PEGs and PEG-like oligomers to anti-PEG antibodies induced by methoxyPEG-proteins

Saifer MG, Williams LD, Sobczyk MA, Michaels SJ, Sherman MR.

The use of methoxypoly(ethylene glycol) (mPEG) in PEG conjugates of proteins and non-protein therapeutic agents has led to the recognition that the polymer components of such conjugates can induce anti-PEG antibodies (anti-PEGs) that may accelerate the clearance and reduce the efficacy of the conjugates. Others have classified anti-PEGs as "methoxy-specific" or "backbone-specific". The results of our previous research on anti-PEGs in the sera of rabbits immunized with mPEG or hydroxyPEG (HO-PEG) conjugates of three unrelated proteins were consistent with that classification (Sherman, M.R., et al., 2012. Bioconjug. Chem. 23, 485-499). Enzyme-linked immunosorbent assays (ELISAs) were performed on rabbit antisera and rabbit monoclonal anti-PEGs with competitors including 10 kDa mPEG, 10 kDa PEG diol and six linear or cyclic oligomers of oxyethylene (CH2CH2O), with molecular weights of ca. 150-264 Da. Our results demonstrate that (1) the binding affinities of anti-mPEGs depend more on the backbone lengths of the polymers and the hydrophobicities of their end-groups than on their resemblance to the methoxy terminus of the immunogenic polymer; (2) anti-PEGs raised against HO-PEG-proteins are not directed against the terminal hydroxy group, but against the backbone; (3) rabbit anti-PEGs bind to and distinguish among PEG-like oligomers with as few as three oxyethylene groups; and (4) none of the monoclonal or polyclonal anti-PEGs was absolutely "methoxy-specific" or "backbone-specific", but displayed distinct relative selectivities. If these results are relevant to human immune responses, the clinical use of stable conjugates of HO-PEG with proteins and non-protein therapeutic agents would be expected to produce fewer and less intense immune responses than those induced by conjugates with mPEG or PEGs with larger alkoxy groups.