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Statistical Analysis of Metabolomics Data

Statistical matters form an integral part of a metabolomics experiment. In this chapter we describe several important aspects in the analysis of metabolomics data such as the removal of unwanted variation and the identification of differentially abundant metabolites, along with a nu ...

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Bryophytes: Liverworts, Mosses, and Hornworts: Extraction and Isolation Procedures

There are more than 20,000 species of bryophytes in the world. Among them, almost of liverworts (Marchantiophyta) possess beautiful blue, yellow colored or colorless cellular oil bodies from which over several hundred new terpenoids, acetogenins, and aromatic compounds including f ...

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Strategies in Biomarker Discovery. Peak Annotation by MS and Targeted LC-MS Micro-Fractionation for De Novo Structure Identification by Micro-NMR

In metabolomic studies the identification of biomarkers is a key step but represents a serious bottleneck since the de novo identification of natural products is a lengthy process. A strategy for the dereplication and peak annotation of plant biomarkers is presented based on high resolut ...

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Bridging the Gap: Basic Metabolomics Methods for Natural Product Chemistry

Natural products and their derivatives often have potent physiological activities and therefore play important roles as both frontline treatments for many diseases and as the inspiration for chemically synthesized therapeutics. However, the detection and synthesis of new the ...

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Metabolomics and Dereplication Strategies in Natural Products

Metabolomic methods can be utilized to screen diverse biological sources of potentially novel and sustainable sources of antibiotics and pharmacologically-active drugs. Dereplication studies by high resolution Fourier transform mass spectrometry coupled to liquid chr ...

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Screening for Antibacterial, Antifungal, and Anti quorum Sensing Activity

The plate-hole diffusion assay is an invaluable screening tool to evaluate the antibacterial potential of natural products. It relies on the diffusion of test material from pre-cut wells through agar seeded with bacteria. Samples that are capable of inhibiting bacterial growth will pro ...

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Screening for Antidiabetic Activities

Screening extracts and drug entities for antidiabetic bioactivity is essentially limited to animal models as the processes leading to hyperglycemia and the complications of diabetes involve more than one organ. Further, in vitro results seldom translate into meaningful in vivo out ...

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Bioassays for Anticancer Activities

The MTT/MTS in vitro cell proliferation assay is one of the most widely used assays for evaluating preliminary anticancer activity of both synthetic derivatives and natural products and natural product extracts. The highly reliable, colorimetric based assay is readily performed on a w ...

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Discovery, Biosynthesis, and Rational Engineering of Novel Enterocin and Wailupemycin Polyketide Analogues

The marine actinomycete Streptomyces maritimus produces a structurally diverse set of unusual polyketide natural products including the major metabolite enterocin. Investigations of enterocin biosynthesis revealed that the unique carbon skeleton is derived from an aro ...

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Natural Product Chemistry in Action: The Synthesis of Melatonin Metabolites K1 and K2

Natural product chemistry often yields new compounds with great potential for economic and/or health benefits. However, most natural compounds must be artificially synthesized on an industrial scale to generate enough active ingredients to be commercially viable. Thus chemical ...

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Determination of Absolute Configuration Using Single Crystal X-Ray Diffraction

Single crystal X-ray crystallography is the most powerful structural method for the determination of the 3D structures of molecules. While the results of a routine diffraction experiment readily provide unambiguous determination of the relative configuration of all stereogen ...

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Extraction Protocol for Nontargeted NMR and LC-MS Metabolomics-Based Analysis of Hard Coral and Their Algal Symbionts

Metabolomics and in particular, nontargeted metabolomics, has become a popular technique for the study of biological samples as it provides considerable amounts of information on extractable metabolites and is ideal for studying the metabolic response of an organism to stressors in ...

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Micro- and Mid-Scale Maleimide-Based Conjugation of Cytotoxic Drugs to Antibody Hinge Region Thiols for Tumor Targeting

Currently, the principal chemistries for the preparation of antibody–drug conjugates (ADC) target either lysines or cysteines for coupling cytotoxic drugs for delivery to target cells expressing tumor-specific antigens. All of these chemistries generate populations of mol ...

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Safe Handling of Cytotoxic Compounds in a Biopharmaceutical Environment

Handling cytotoxic drugs such as antibody–drug conjugates (ADCs) in a biopharmaceutical environment represents a challenge based on the potency of the compounds. These derivatives are dangerous to humans if they accidentally get in contact with the skin, are inhaled, or are ingested, ei ...

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Pharmacokinetics and ADME Characterizations of AntibodyDrug Conjugates

Pharmacokinetic and absorption, distribution, metabolism, and excretion (ADME) characterization of antibody–drug conjugates (ADCs) reflects the dynamic interactions between the biological system and ADC, and provides critical assessments in lead selection, optimiz ...

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In Vivo Testing of Drug-Linker Stability

Antibody-drug conjugates (ADCs) are promising biotherapeutics designed to selectively deliver highly cytotoxic drugs to tumor cells while sparing normal tissues. They can be viewed as prodrugs, stable in the bloodstream in order to minimize drug release in circulation and efficie ...

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Linker Technologies for AntibodyDrug Conjugates

Antibody–drug conjugates (ADCs), which combine the specificity, favorable pharmacokinetics, and biodistribution of a monoclonal antibody (mAb) with the cytotoxic potency of a drug, are promising new therapies for cancer. Along with the development of monoclonal antibodies (mA ...

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AntibodyDrug Conjugate Payloads

Toxin payloads, or drugs, are the crucial components of therapeutic antibody–drug conjugates (ADCs). This review will give an introduction on the requirements that make a toxic compound suitable to be used in an antitumoral ADC and will summarize the structural and mechanistic features of ...

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Selecting an Optimal Antibody for AntibodyDrug Conjugate Therapy: Internalization and Intracellular Localization

Antibody–drug conjugates (ADCs) combine the selectivity of a monoclonal antibody with the killing potency of a cytotoxic drug. For an antibody to function as a successful component of an ADC, it needs to bind to the target antigen on the surface of tumor cells and then be internalized by the cell. Follo ...

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AntibodyDrug Conjugate Target Selection: Critical Factors

ADC success requires that all three components of the agent function in a near-flawless manner. Equally important is that the target be selected with stringent consideration as the target is the one factor in ADC development that is immutable and beyond the reach of the developer to refine/mani ...

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