Tag: PEGylation reagent

Three Click Chemistry Ideas for PEGylation Reagents

Have you ever been working your way through a product catalog and encountered a product you weren’t sure how to use? I know I have. It helps in those moments of “What do I do with this?” to have some tips on how to use a product effectively. Today I want to take one of our unique click chemistry discrete PEGylation (dPEG®) reagents, PN10524, azido-dPEG®11-amine, and offer three ideas on how to get the most out of it in an application. Continue reading

Title Slide of Paul Davis' talk at the 7th Annual World ADC Summit in San Diego, given October 11, 2016. The talk is titled "Using the dPEG as the Framework to Uniquely Load and Protect Payloads in an ADC Format with dPEG Single Molecule Precision"

Our World ADC 2016 Presentation

The World ADC Summit in San Diego was held October 10-13, 2016. This was the 7th Annual World ADC Summit. On October 11, 2016, our company president, Paul D. Davis, presented his talk titled, “Using the dPEG® as the Framework to Uniquely Load and Protect Payloads in an ADC Format …with dPEG® single molecule precision.” Continue reading

Chemical structure of PN10283, Fmoc-N-amido-dPEG®12-acid

SNARE-Mediated Membrane Fusion and dPEG®, Part 1

Part 1: A Reduced SNARE Model for Membrane Fusion

The cells of all living things depend on membrane fusion for intra- and intercellular transport of molecules. In both cellular membrane fusion and intracellular vesicle fusion, the fusion process is controlled and guided by SNARE proteins. SNARE is an acronym for Soluble NSF Attachment Protein Receptor. NSF stands for N-ethylmaleimide-Sensitive Factor. Reviews of SNARE protein structure and function can be found here, here, here, and here. An example of a SNARE protein is synaptobrevin. Click part 2 and part 3 to read the other pieces in this series. Continue reading

Chart showing the analgesic activities of various galanin analogues used in a formalin pain assay.

PEGylated Galanin Shows Enhanced Analgesic Effects in PNS

Galanin is a naturally occurring neuropeptide in the human body that facilitates communication between cells to balance a myriad of physiological functions. Neuropeptides are biosynthesized molecules used by the human body for everything from neurogenesis to cell communication.  Galanin’s main receptor sites reside in the central nervous system (CNS), and it normally crosses the blood brain barrier; however, the peripheral nervous system (PNS) also reacts directly to galanin and its receptors in sites of pain mediation.1  Continue reading

dPEG®-Modified Diabodies Improve Tumor Imaging

Researchers in Australia and the United States have shown that dPEG®-modified diabodies improve positron emission tomography (PET) imaging of tumors by reducing kidney uptake of diabody and extending diabody half-life in the bloodstream, which thus allows more diabody to be taken up by the tumor.1 These findings suggest that better tumor imaging can be achieved using less material, because more of the diabody that targets the tumor gets to the tumor and less of it is excreted by the kidney. Continue reading

Label monoclonal antibodies site specifically with ETAC reagents

ETAC and labeling monoclonal antibodies

Monoclonal antibodies and their small fragments (Fabs, scFv, diabodies etc.) are intriguing objects for creation of protein-based medicines. These proteins can be site-specifically modified with ETAC-dPEG® (“ETAC” abbreviates “Equilibrium Transfer Alkylation Cross-link”; “dPEG®” is the registered trade name for “discrete Poly(Ethylene Glycol)”) reagents. Using ETAC, a three-carbon bridge is formed linking the two cysteine sulfur atoms. The dPEG® attached to the ETAC reduces the protein’s immunogenicity and prevents rapid clearance of the protein from the bloodstream. This, in turn, helps to maintain a desired therapeutic concentration between doses, thereby reducing the risk of loss of efficacy. The structure of ETAC-reagent and generation of the dPEG®-monosulfone which undergoes a site-specific conjugation with a Fab are outlined below in Figure 1. For details, see, for example, “Comparative binding of disulfide-bridged PEG-Fabs”, Bioconjugate Chemistry (2012), 23, 2262-2277; and “Disulfide bridge based PEGylation of proteins”, Advances in Drug Delivery Reviews (2008), 60, 3-12.
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Superior Surface Protection of Gold Nanoparticles With Short-Chain PEG

Surface protection of gold nanoparticles is improved by using short-chain, alcohol-terminated dPEG® linkers rather than (2-mercaptopropanoyl)glycine (tiopronin) or mercapto-undecyl-tetraethyleneglycol, according to research findings from the lab of David E. Cliffel, Department of Chemistry, Vanderbilt University. Short-chain dPEG®s increase water solubility, are non-toxic, and show no immune response to anti-PEG antibodies at low concentrations.(1) Continue reading

Organophosphorus Hydrolase Pharmacokinetics and Immunogenicity are Improved by Branched dPEG®

Organophosphorus hydrolase  (OPH, EC 8.1.3.1), also known as Aryldialkylphosphatase, is a remarkably stable homodimeric enzyme that can detoxify organophosphate compounds. Organophosphate compounds are the basis of numerous pesticides (e.g., malathion) and chemical warfare weapons (e.g., sarin, VX). Organophosphates act by blocking the action of the enzyme acetylcholinesterase. Overuse and misuse of organophosphate pesticides are major causes of acute pesticide poisoning and death. See also here. Continue reading

A dPEG®ylated Avibody provides an example of the discrete nature of Quanta BioDesign's dPEG® reagents..

Noise control and removal through dPEG®ylation

Noise control and removal is important in any discipline where clean, clear signals are critical in measurement and data collection. For this reason, whilst the saying ‘Beauty is in the eyes of the beholder’ may be true in many instances, scientific research cannot permit subjective, qualitative thinking to trump objective data. Continue reading