Amine-reactive pyridylhydrazone-based PEG reagents for pH-reversible PEI polyplex shielding

Amine-reactive pyridylhydrazone-based PEG reagents

PEGylation which is reversed after the therapeutic agent reaches the target cell presents an attractive feature for drug, protein or nucleic acid delivery. Amine-reactive, endosomal pH cleavable polyethylene glycol aldehyde-carboxypyr-idylhydrazone, N-hydroxysuccinimide esters (PEG-HZN-NHS) were synthesized and applied for bioreversible surface shielding of DNA polyplexes. Monofunctional mPEG-HZN-NHS was synthesized by reacting succinimidyl hydraziniumnicotinate with mPEG-butyraldehyde (20kDa). … [Read more…]

In vitro and in vivo efficacy of PEGylated diisopropyl fluorophosphatase (DFPase)

PEGylation mpeg-sc

Highly toxic organophosphorus compounds that irreversibly inhibit the enzyme acetycholinesterase (AChE), including nerve agents like tabun, sarin, or soman, still pose a credible threat to civilian populations and military personnel. New therapeutics that can be used as a pretreatment or after poisoning with these compounds, complementing existing treatment schemes such as the use of atropine … [Read more…]

Structural identification and biological activity of positional isomers of long-acting and mono-PEGylated recombinant human granulocyte colony-stimulating factor with trimeric-structured methoxy polyethylene glycol N-hydroxysuccinimidyl functional group


The individual positional isomers from the mono-PEGylated recombinant human granulocyte colony-stimulating factor (rhG-CSF) were successfully isolated with additional strong cation exchange chromatography using Source 15S. The three isolated individual positional isomers were found to be homogeneous by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), analytical size exclusion high-performance liquid chromatography (SE-HPLC), and analytical cation exchange … [Read more…]

Nonfouling Hydrophilic Poly(ethylene glycol) Engraftment Strategy for PDMS/SU-8 Heterogeneous Microfluidic Devices


We report a novel nonfouling passivation method using poly(ethylene glycol) (PEG) engraftment on the surfaces of poly(dimethylsiloxane) (PDMS) microfluidic devices sealed with SU-8. To achieve bonding between the PDMS and SU-8 surfaces, the PDMS surface was first functionalized with amines by treatment with 3-amino-propyltrimethoxysilane (APTMS) for subsequent reaction with epoxide functional groups on SU-8 surfaces. … [Read more…]

PEGylation of Concanavalin A to Decrease Non-Specific Interactions in a Fluorescent Glucose Sensor

PEGylation of Concanavalin A

The ability of people with diabetes to both monitor and regulate blood sugar levels is limited by the conventional “finger-prick” test that provides intermittent, single point measurements. Toward the development of a continuous glucose monitoring (CGM) system, the lectin, Concanavalin A (ConA), has been utilized as a component in a Forster resonance energy transfer (FRET), … [Read more…]

PEGylated Polyethylenimine as Enhanced T-1 Contrast Agent for Efficient Magnetic Resonance Imaging


Currently used small molecular magnetic resonance (MR) imaging contrast agents (CM) in clinics have relatively short half-lives, which has limited the acquisition of high-resolution organ and angiographic images. Therefore, development of a facile strategy for the synthesis of long-circulating CAs with the transforming potential for MR imaging still remains a great challenge. Here we communicate … [Read more…]

Polylysine-PEG copolymer barriers with dual character of both adsorption to tissue and prevention of cell adhesion


The biocompatible barriers with dual character for surface active agents like biosurfactants were made by reacting cationic polylysine(PL) with nonionic poly(ethylene glycol) (PEG) to give block and graft PL-PEG copolymers, PL-h-PEG and poly-L-lysine (PLL)-g-PEG. In particular, PL-b-PEG block copolymers were synthesized by a new method using an activated succinimidyl ester of carboxymethylated MPEG(SCM–MPEG) and a … [Read more…]

PEGylation and pharmacological characterization of a potential anti-tumor drug, an engineered arginine deiminase originated from Pseudomonas plecoglossicida

PEGylation and pharmacologica

Arginine deiminase (ADI) has been studied as a potential anti-cancer agent for arginine-auxotrophic tumors. PEGylation is one of the best methods to formulate a bioconjugated protein with extended physical stability and reduced immunogenicity. Here, PEGylation and pharmacological properties of an engineered ADI originated from Pseudomonas plecoglossicida were studied. Among polyethylene glycol (PEG) reagents with succinimidyl … [Read more…]

Impact of pegylation on biopharmaceutical properties of dendrimers


In the recent years, conjugation of polyethylene glycol (PEG) on dendrimer has become an established and highly refined technology for delivery of bioactives. Dendrimers provide an ideal platform for delivery of bioactive as they represent well-defined, highly branched, nanoscale architecture with several modifiable surface groups. However, the actual potential of dendrimers is not realized due … [Read more…]

Islets immunoisolation using encapsulation and PEGylation, simultaneously, as a novel design


The most important obstacle in islets transplantation for the treatment of diabetes is graft rejection by the host immune system. To solve this problem, immunosuppressive drugs should be used, but they may have several side effects. To overcome these problems, islets immunoisolation systems such as encapsulation and PEGylation have been developed. The aim of this … [Read more…]

PEGylation of recombinant hirudin in mixed aqueous–organic solutions


Serious loss of polyethylene glycol (PEG) reagent is confronted during PEGylation of proteins in mildly acidic aqueous solution. In this study, a novel approach of PEGylation of recombinant hirudin variant-2 (HV2) with monomethoxy-PEG-succinimidyl carbonate (mPEG-SC) was developed in six mixed aqueous–organic solutions. The PEGylation efficiency in each mixed solutions was greater than that in pure … [Read more…]

PEGylation of the peptide Bac7(1–35) reduces renal clearance while retaining antibacterial activity and bacterial cell penetration capacity


The proline-rich antibacterial peptide Bac7(1–35) protects mice against Salmonella typhimurium infection, despite its rapid clearance. To overcome this problem the peptide was linked to a polyethylene glycol (PEG) molecule either via a cleavable ester bond or via a non-hydrolysable amide bond. Both the PEGylated conjugates retained most of the in vitro activity against S. typhimurium. In addition, … [Read more…]

Moderate PEGylation of the carrier protein improves the polysaccharide-specific immunogenicity of meningococcal group A polysaccharide conjugate vaccine


Neisseria meningitidis can cause severe and fulminant diseases such as meningitis. Meningococcal capsular polysaccharide (PS) is a key virulence determinant that is not able to induce immunological memory. Conjugation of PS to a carrier protein can significantly increase the immunogenicity of PS and induce immunological memory. Due to the classically described carrier-induced epitopic suppression (CIES) … [Read more…]

PEGylation of carbon nanotubes via mussel inspired chemistry: Preparation, characterization and biocompatibility evaluation


A novel strategy for surface modification of multi-walled carbon nanotubes (MWCNT) was developed via combination of mussel inspired chemistry and Michael addition reaction. In this procedure, pristine MWCNT were first coated with polydopamine (PDA) through self polymerization of dopamine. The PDA functionalized CNT (CNT-PDA) were further functionalized with amino-terminated polymers (polyPEGMA), which were synthesized via … [Read more…]

PEGylation of alpha-momorcharin: synthesis and characterization of novel anti-tumor conjugates with therapeutic potential

pegylation method

Alpha-momorcharin (α-MMC) is a ribosome-inactivating protein (RIP) with excellent cytotoxicity to tumor cells. However, its strong immunogenicity and short plasma half-life limit its clinical applications. To overcome this, we have to PEGylated α-MMC using a branched 20 kDa (mPEG) 2-Lys-NHS. Homogeneous mono-, di- and tri-PEGylated α-MMCs were synthesized, purified and characterized. In vitro and in vivo … [Read more…]

Screening of Reducing Agents for the PEGylation of Recombinant Human IL-10


PEGylation is a technology commonly used to enhance the bioavailability of therapeutic proteins in patients. Reductive alkylation of a protein amino terminal alpha amine in the presence of a polyethylene glycol (PEG) chain derivatized with propionaldehyde and a reducing agent, typically sodium cyanoborohydride, is one of the technologies available to achieve quantitative and site specific … [Read more…]

Optimization of PEGylation Conditions for BSA Nanoparticles Using Response Surface Methodology

PEGylation drug

Chemical coupling of polyethylene glycol (PEG) to proteins or particles (PEGylation), prolongs their circulation half-life by greater than 50-fold, reduces their immunogenicity, and also promotes their accumulation in tumors due to enhanced permeability and retention effect. Herein, phase separation method was used to prepare bovine serum albumin (BSA) nanoparticles. PEGylation of BSA nanoparticles was performed … [Read more…]

Extension Arm Facilitated PEGylation of Hemoglobin: Correlation of the Properties with the Extent of PEGylation

utop peg

Human hemoglobin (Hb) conjugated with six copies of PEG-5K is nonhypertensive. The hexaPEGylated Hb exhibits molecular size homogeneity in spite of the chemical heterogeneity with respect to the sites of conjugation. In the present study, Hb conjugated with an average of 4, 6, 8 and 10 copies of PEG-5K chains have been generated using the … [Read more…]

PEGylation Prevents the N-Terminal Degradation of Megakaryocyte Growth and Development Factor

Utopbio PEGylation

PEGylation of proteins is commonly performed to achieve increased in-vivo circulation half-lives. For rHuMGDF, an additional advantage of PEGylation was enhancedin-vitro shelf-life stability. Determine the effect of PEGylation on in-vitro degradation for recombinant human Megakaryocyte Growth and Development Factor (rHuMGDF) in the neutral pH range. Degradation products were characterized by cation-exchange HPLC, N-terminal sequencing and … [Read more…]

The impact of PEGylation on biological therapies

The impact of PEGylation on biological therapies

The term PEGylation describes the modification of biological molecules by covalent conjugation with polyethylene glycol (PEG), a non-toxic, non-immunogenic polymer, and is used as a strategy to overcome disadvantages associated with some biopharmaceuticals. PEGylation changes the physical and chemical properties of the biomedical molecule, such as its conformation, electrostatic binding, and hydrophobicity, and results in … [Read more…]

Effects of pharmaceutical PEGylation on drug metabolism and its clinical concerns

PEGylation and drug

PEGylation refers to covalent conjugation of one or more polyethylene glycol chains to a drug molecule. It also refers to formulation of a drug into PEGylated drug-delivery vehicles in pharmacy. It is well-known that PEGylation can greatly influence the pharmacokinetics and pharmacodynamics of drugs. PEGylation is an effective approach to potentiate drugs with undesirable properties. … [Read more…]

Mechanistic Insights into the Stabilization of srcSH3 by PEGylation


Protein PEGylation (attaching PEG chains to proteins) has been widely used in pharmaceuticals and nanotechnology. Although it is widely known that PEGylation can increase the thermodynamic stability of proteins, the underlying mechanism remains elusive. In this Article, we studied the effect of PEGylation on the thermodynamic and kinetic stability of a protein, SH3. We show … [Read more…]

An oriented adsorption strategy for efficient solid phase PEGylation of recombinant staphylokinase by immobilized metal-ion affinity chromatography

Technology of PEGylation

Conjugation of truncated recombinant staphylokinase (trSak) with polyethylene glycol (PEG) is an effective way to overcome its short plasma half-life and enhance its therapeutic potential. However, conventional amine directed PEGylation chemistry inevitably led to modification at its functionally important N terminus, which resulted in a significantly reduced bioactivity of trSak. In this study, a novel … [Read more…]

N-terminal specificity of PEGylation of human bone morphogenetic protein-2 at acidic pH

N-terminal specificity of PEGylation

Site-specific PEGylation offers the possibility to modify a therapeutic protein without interfering with its biological activity. Previously, a preferential N-terminal PEGylation has been reported for several proteins when the reaction was performed at acidic pH. In the present study it was explored if acidic pH favors N-terminal PEGylation of bone morphogenetic protein-2 (BMP-2). PEGylation by … [Read more…]

PEGylation of recombinant hirudin in mixed aqueous-organic solutio

PEGylation of recombinant hirudin in mixed aqueous-organic solutions

Serious loss of polyethylene glycol (PEG) reagent is confronted during PEGylation of proteins in mildly acidic aqueous solution. In this study, a novel approach of PEGylation of recombinant hirudin variant-2 (HV2) with monomethoxy-PEG-succinimidyl carbonate (mPEG-SC) was developed in six mixed aqueous-organic solutions. The PEGylation efficiency in each mixed solutions was greater than that in pure … [Read more…]

State of the art in PEGylation: The great versatility achieved after forty years of research


In the recent years, protein PEGylation has become an established and highly refined technology by moving forward from initial simple random coupling approaches based on conjugation at the level of lysine epsilon-amino group. Nevertheless, amino PEGylation is still yielding important conjugates, currently in clinical practice, where the degree of homogeneity was improved by optimizing the … [Read more…]

Site-Specific PEGylation at Histidine Tags

Site-Specific PEGylation at Histidine Tags

The efficacy of protein-based medicines can be compromised by their rapid clearance from the blood circulatory system. Achieving optimal pharmacokinetics is a key requirement for the successful development of safe protein-based medicines. Protein PEGylation is a clinically proven strategy to increase the circulation half-life of protein-based medicines. One limitation of PEGylation is that there are … [Read more…]