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Schematic drawing of a TOPO coated green quantum dot, approximately 3 nm in diameter.

dPEG® Eliminates Non-Specific Binding on Quantum Dots

What about Quantum Dots?

Let’s start with a quick refresher. Quantum dots are cool little tiny nano particles, less than 10 nm in diameter, made of a semiconductor alloy core and coated with a shell of a different alloy, which fluoresce at different wavelengths depending on their size and specific composition. The smaller the quantum dot, the more blue-shifted its emission wavelength while larger quantum dots (6 nm and larger) shift to red and near-IR. Quantum dots can be a good alternative to organic dyes since they have broad excitation spectra (absorb energy at a wide range of wavelengths), narrow emission spectra (emit a fairly specific wavelength), and don’t suffer from photobleaching (degradation due to light intensity/oxidizing agents). Read more about fluorescence excitation and emission.

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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 

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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.

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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)

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Thiol Reactive Crosslinkers for Bioconjugation

Thiol reactive crosslinkers are one of the most common classes of crosslinkers in bioconjugation (1). The popularity of conjugation to a thiol is due in part to its presence in many proteins, but they are not as prevalent as amines, which are another site for conjugation. This will allow for greater control of the conjugation. Even greater control of the conjugation process is afforded if a thiol reactive compound is combined with an amine reactive compound to create a heterobifunctional crosslinker.

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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.

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