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…
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…
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…
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, organ transplants, some cancer treatments) are especially at risk. An estimated 1.5-2 million people die each year from systemic fungal infections (1). Despite its “gold standard” label, there are several difficulties with Amphotericin B.
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.
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.
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.
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.