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Aptamer-Drug Conjugates Design

What is Aptamer-Drug Conjugates?

Aptamer protac is a functional nucleic acid that can recognize and bind target substances with high specificity and affinity, and can be obtained by Systematic Evolution of Ligands by Exponential Enrichment (SELEX) technique screening, with sequence length mostly between 15 and 60 bases.

Aptamer-drug conjugates (ApDCs) are a form of drug conjugates that uses a structured oligonucleotide sequence (aptamer) as the target molecule. Aptamers are referred to as “chemical antibodies” and have similar targeting and target binding capabilities to antibodies. Aptamers can be loaded with therapeutic cargoes (drugs) such as chemotherapeutics, photosensitizers, photothermal agents, immunotherapeutics, RNA, enzymes, or even bifunctional combination molecules (e.g. Aptamer PROTAC, LYTAC).

Features of ApDCs using aptamer as a targeting molecule: (1) Wide range of targets: Targets include metal ions, amino acids, nucleotides, growth factors, proteins, viruses, bacteria, living cells, and living organisms, etc.

(2) High affinity and high specificity: Aptamers with high specificity that recognize only the target molecule but not other molecules can be obtained during the screening process.

(3) Good stability: Aptamers have good chemical stability and thermal stability, and are also convenient for preservation and transportation. In addition, after special modification, the aptamer has better stability and longer half-life.

(4) Low immunogenicity: The aptamer has low molecular weight and small size, which can easily cross the tissue barrier and reach the site of action quickly, and also be easily cleared by the metabolic organs in the body, so it has low immunogenicity and toxicity.

(5) Easy to prepare and modify: Aptamers are synthesized rapidly and in large quantities in vitro by chemical synthesis methods such as DNA synthesis technology, PCR technology or RNA in vitro transcription, and are reproducible from batch to batch.

Why Aptamer-Drug Conjugates? Aptamer-PROTAC Conjugates The development of proteolysis-targeting chimeras (PROTAC) is a promising strategy for targeted protein degradation. However, PROTAC heterobifunctional molecules are usually limited by poor membrane permeability, low in vivo potency, and inhomogeneous distribution. Therefore, aptamer-PROTAC conjugates may serve as a novel strategy. By coupling PROTAC to aptamers through cleavable linkers, aptamer-PROTAC conjugates could show improved targeting ability with the potential to enhance target protein degradation and reduce off-target toxicity compared to unmodified PROTAC.

Aptamer-LYTAC Conjugates Lysosome-targeting chimera (LYTAC) is a promising technology to extend the scope of target proteins to extracellular targets. However, LYTACs have high uncertainty in number and location, high molecular weight and low internalization efficiency. Aptamer-LYTAC conjugates could serve as a novel solution to avoid these problems. The specific degradation of extracellular and membrane proteins could be achieved by binding the aptamer to tri-GalNAc. It is worth mentioning that aptamers have the advantage of easy synthesis and low molecular weight. Aptamer-LYTAC conjugates are expected to expand the use of aptamers and provide new insights into targeted protein degradation.

Services of Aptamer-Drug Conjugates Design Aptamer synthesis and screening Conjugation chemical methods (optional) Aptamer-drug conjugates synthesis and characterization Linker design and optimization

Source: https://ptc.bocsci.com/services/aptamer-drug-conjugates-design.html

Chemical Products - Isotope BOC

BOC Sciences is committed to providing customers with isotope-labeled vitamins. We offer a complete range of labeled vitamins standards. All products come with comprehensive analytical data files and are of high chemical purity.

Stable isotope labeled vitamins are safe and stable, non-radioactive and have a long half-life. Their mass spectra differ from their unlabeled counterparts, making them traceable for use as internal standards or tracking reagents for the analysis of vitamin uptake and metabolism. Over recent years, stable isotope labelled vitamins are the gold standard with regard of quantifying endogenous vitamin metabolites in complex biological matrices. A range of stable isotope labeled vitamins, including 2H, 13C, 15N, and 18O labeled vitamins, are currently used extensively for metabolic and pathophysiological explorations and for the assessment of disease biomarkers.

Background Vitamins are a group of organic compounds that are essential for good health and play an important regulatory role in the metabolism of substances. If a vitamin is deficient for a long period of time, it can cause physiological disorders and lead to the development of certain diseases. They are generally obtained from food. There are dozens of them found at this stage, such as vitamin A, vitamin B complex, vitamin C, etc.

Application of Stable Isotope Labeled Vitamin B The B vitamins are the basic substances that drive the conversion of all substances in the body into energy. They are involved in the metabolism of proteins, carbohydrates and fats, and are also essential for promoting the body's metabolism. As internal standards, stable isotope labeled thiamine, riboflavin, niacinamide, pyridoxine show the potential for the simultaneous determination of total vitamins B1, B2, B3 and B6 in infant foods and related nutritional products. A stable isotope labeling method based on essential nutrients in cell culture, including isotopically labeled niacinamide, is used to efficiently label the intracellular NAD(H) and NADP(H) pools. The method is combined with liquid chromatography high resolution mass spectrometry to track and quantify the metabolism of NAD(H) and NADP(H) in cells and tissues.

Application of Stable Isotope Labeled Vitamin C Stable isotope labeled ascorbic acid has good stability and safety in vivo. Also, due to its enrichment behaviour in the body with minimal correlation to endogenous ascorbic acid, it has been widely used to identify and differentiate between freshly absorbed and endogenous vitamins in humans and thus to determine the pharmacokinetic properties of ascorbic acid. It can also be used for investigating the possible effects of other dietary components, such as ferrous ions and grape juice, on ascorbic acid absorption and metabolism in healthy adult subjects.

Application of Stable Isotope Labeled Vitamin E Similarly, trideuterated α-tocopherol is used as an internal standard to assess overall vitamin E levels in humans by MS measurements. In addition, this stable isotope labeled vitamin E hydrolysis product can be used to study the kinetics of vitamin E metabolism in organisms exposed to oxidative stress and stressful environments (e.g. chronic inflammation, smoking, radiation, etc.).

Source: https://isotope.bocsci.com/products/labelled-vitamins-3842.html