Biological activities in vivo

In other cases, the widespread application of a biopharmaceutical may be hindered by the occurrence of relatively toxic side effects (as is the case with tumour necrosis factor a (TNF-a, Chapter 9). Finally, some biomolecules have been discovered and purified because of a characteristic biological activity that, subsequently, was found not to be the molecule s primary biological activity. TNF-a again serves as an example. It was first noted because of its cytotoxic effects on some cancer cell types in vitro. Subsequently, trials assessing its therapeutic application in cancer proved disappointing due not only to its toxic side effects, but also to its moderate, at best, cytotoxic effect on many cancer cell types in vivo. TNF s major biological activity in vivo is now known to be as a regulator of the inflammatory response. 

Also, the interaction of these nucleosides with cellular constituents of intact L1210 leukemia cells was studied.76 Rapid reaction with plasma membrane and soluble, intracellular thiols was demonstrated, as well as a good correlation between the extent of plasma membrane alkylation in vitro and the biological activity in vivo. 

The water-soluble vitamins are a highly diverse group of compounds with differing physicochemical properties. A single vitamin generally consists of several vitamers, or chemical species, each of which exhibits the same biological activity in vivo. Individual vitamers with the same biological functions often exhibit vastly different physicochemical properties. This necessitates unique extraction and separation procedures for each vitamin. As a result, each vitamin is considered individually in this chapter. A section on methods that determine multiple vitamins simultaneously is also included. 

The topic of polymorphism is of tremendous and increasing academic and industrial importance in modern crystal chemistry and crystal engineering. The industrial interest stems from the pharmaceutical industry and has stimulated wide-ranging academic study. Legally, a molecule (termed an active pharmaceutical Ingredient, API) with particular biological activity in vivo can be patented as a new invention. Moreover, particular crystal forms of that molecule (polymorphs) can be separately patented as distinct inventions. If particular polymorphs are patented after the original API patent then upon the... 

Jain S., D. H. Hreczuk-Hirst, B. McCormack, M. Mital, A. Epenetos, P. Laing, and G. Gregoriadis. 2003. Polysialylated insulin synthesis, characterization and biological activity in vivo. Biochim. Bio-phys. Acta 1622 42-49. 

Both of these objectives are achievable provided the delivery (transport) properties of the drug are improved while maintaining its biological activity in vivo. In this context, the parent drug properties, such as lipid solubility, aqueous solubility, partition coefficient, and chemical and metabolic stability, are optimized, often in a balanced combination. 

Triadimenol has been shown to be biologically active in vivo against a number of fungal diseases in plants, the spectrum of activity being particularly useful in the control of seed-borne and foliar dieases of cereals (Frohberger, 1978 T ragner-Born and Boom, 1978 Wainwright et al., 1979). 

For only one of the recently introduced pestiddes convincing evidence is available that inhibition of mitochondrial ATP synthase is responsible for its biological activity in vivo and therefore represents its mode of action The insecticide and acaridde diafenthiuron (1) (Fig. 28.1.1). 

Substituted-phenyl-5-isoxazolecarboxaldehydes have been identified as activated aldehydes for the generation of isoxazole-based combinatorial libraries in the solid (Scheme 3.206) and solution phase (Scheme 3.207). The highly functionalized isoxazole-based libraries have been synthesized in parallel format using the MBH reaction and Michael addition. With an objective of lead generation, the libraries have been evaluated for their biological activities in vivo. 

R. Satake-Ishlkawa, M. Ishikawa, Y. Okada, M. Kakitani, M. Kawagishi, S. Matsuki, K. Asano, Chemical modification of recombinant human granulocyte colony-stimulating factor by polyethylene glycol increases its biological activity in vivo. Cell Struct. Funct., 17 (3) 157-160, 1992. 

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