The Critical Importance of Linker Chemistry for Antibody-Drug Conjugates (ADCs)
ADC Chemical Linkers Are Vital The covalent conjugation of monoclonal antibodies (mAbs) and cytotoxic drugs, known as antibody-drug conjugates (ADCs), is rapidly becoming a powerful component of cancer treatment. Hundreds of thousands of research articles and reviews are readily accessible on the World Wide Web, reporting and discussing ADCs in varying levels of detail. However, while much attention has been…
Marvelous Maleimide Crosslinker Products
Click Here for a Downloadable PDF of This Review! This review discusses Quanta BioDesign's maleimide crosslinker products - what they do and when you might want to use them. Our discrete maleimide PEG crosslinker products are consistently our best-selling products. Similarly, our maleimide informational pages are our most frequently visited pages on this website. That's great news to us! We…
Aminooxy-dPEG®11-azide: A New Click Chemistry Crosslinker
Quanta BioDesign, Ltd. is proud to announce that our newest click chemistry crosslinker, Aminooxy-dPEG®11-azide∙HCl, product number 10538, is available for sale. This crosslinker combines carboxyl reactivity via an aminooxy group and alkyne reactivity through an azide group. See Figure 1 for the structure. An azide group sits at one end of a 38 atom (40.8 Å) discrete polyethylene glycol (dPEG®)…
Three Click Chemistry Crosslinking Ideas with dPEG®
Have you ever been working your way through a product catalog when you've come across a product you weren't sure how to use? I know I have. In those "What do I do with this?" moments, tips that explain how to use a product effectively really help me. In this post, I offer three ideas on how to use one…
Copper-free Click Chemistry to Crosslink Azides and Amines
Quanta BioDesign's monodispersed, discrete PEG (dPEG®) products include a wide range of useful tools for click chemistry. Most of our reagents are designed to enable copper-free click chemistry, which is essential for biocompatible labeling and crosslinking. Copper-free click chemistry that allows crosslinking of an amine to an azide is the subject of this post. If you are unsure what a…
Extracellular Drug Conjugates Therapeutically Exploit Protein Proximity
Pharmaceutical company Centrose, founded by James R. Prudent, Ph.D., developed a new class of antibody drug conjugates called extracellular drug conjugates. Nature Publishing Group published the research as a open access paper in its Molecular Therapy journal.1 Apart from the interesting and important development of a new class of antibody drug conjugate (ADC), the research also showed how important linker length 2 is…
Amphotericin B+dPEG®: Water-Soluble, Less Toxic, Potent
About Amphotericin B Amphotericin B (Figure 1) is the "gold standard" treatment for systemic fungal infections and diseases caused by the parasite Leishmania. Sometimes it is the only effective treatment because drug resistance renders other treatments useless. Systemic fungal infections are an increasingly serious, widespread problem in medicine. Patients with weakened or suppressed immune systems (caused by HIV/AIDS, diabetes,…
SNARE-Mediated Membrane Fusion and dPEG®, Part 3
Part 3: Modeling Membrane Fusion with SNARE Protein Analogs Click the links for Part 1 and Part 2 of this three-part series. Membrane fusion is a universal process in living organisms and is critical to proper cellular function. Examples of membrane fusion events include exocytosis, fertilization, envelopment of infecting viruses, and transport of proteins through the Golgi stack. Though essential,…
SNARE-Mediated Membrane Fusion and dPEG®, Part 2
Part 2: Controlling Liposome Fusion Using SNARE Protein Mimics For Part 1 of this three-part series, click here. For part 3, click here. Introduction Continuing earlier work, researchers at the laboratory of Alexander Kros examined the parameters that affect membrane fusion in liposomes composed of the minimal model developed in their earlier paper (1). In this paper (2), the research…
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.…
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…
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…
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…
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…
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) Surface protection and opsonization Tiopronin and mercapto-undecyl-tetraethyleneglycol…
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…
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…
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. Quality data are the basis of all good research.…
Synthetic Allergens for Studying Type-1 Hypersensitivity
Incorporating one of Quanta BioDesign's dPEG® linkers, Notre Dame researchers created novel synthetic allergens for investigating mast cell degranulation. Researching type-1 hypersensitivity (allergic reactions) under laboratory conditions in a way that reflects hypersensitivity in the wild is challenging because in natural conditions epitopes (the part of an antigen recognized by an immune system) are heterogeneous, and the IgE antibodies formed to…
A Better Catalyst for Oxime-Based Bioconjugations
Imine-based reactions leading to the formation of hydrazone or oxime bonds are becoming increasingly important in the conjugation of complex biomolecules. The reaction of an aldehyde or ketone with a hydrazide (for example, Quanta BioDesign product number 10219, Biotin-dPEG®4-hydrazide) leads to the formation of a hydrazone. The reaction of an aldehyde or ketone with an oxyamine (for example, Quanta…