Design active compounds isolation

In 1958 Hanson and Fittkau (HI) published their new method designed for the isolation of polypeptide compounds from urine. Using this method, they isolated more than ten peptides starting with 83 liters of normal urine. The general outline of the method was as follows urine was treated with activated carbon and the adsorbed substances eluted with aqueous acetone containing hydrogen sulfide. The effluent was then... 

S. antibioticus produces another unusual macrolide antibiotic [45] called chlorothricin (57) containing, in addition to the aglycone (modified methylsalicylic acid), saccharides, dideoxyhexoses in the first place. Their biosynthesis was investigated by the incorporation of stable isotopes [45-47]. The compounds were only active in a synthetic medium and inactive in a complex one [48]. Compounds designated MC031-034 (58-61) are similar to chlorothricin mentioned above and were isolated from the cultivation broth of Streptomyces sp. collected in Japan. Another compound, 2-hydroxychlorothricin (62), with antitumor activity, was isolated [66] from Streptomyces K818. 

Lovastatin works by inhibiting 3-hydroxy-3-methylglutary 1 coenzyme A (HMG-(3oA) reductase, a key rate-limitingenzyme in the cholesterol biosynthetic pathway. However, the first specific inhibitors of this enzyme were discovered several years earlier by Endo et al. at Sankyo (157). The compounds, which are structurally related to lovastatin, were isolated from Penicillium citrinum and shown to block cholesterol synthesis in rats and lower cholesterol levels in the blood. Development of the most active compound, designated ML-236B (123), is believed to have been curtailed because of toxicity problems (158). 

As pharmaceutical products contain increasingly potent active constituents and as health, safety, and environmental protection issues increase in importance, isolators have been developed in many shapes and forms to permit thesafe weighing and subdivision of highly active compounds. The most sophisticated applications, such as the subdivision of bulk sterile active compounds, require that the isolator maintain aseptic processing conditions internally at the same time as satisfying the safety requirements. Fig. 2 shows an isolator device designed to allow a keg of potent... 

Isolated bag houses designed with breathing air, decontamination showers, and floor drains with shunt valves that allow waste water to be pretreated should be considered for dealing with highly active compounds. 

Rebek and coworkers have also recently published a procedure for the synthesis of libraries of small organic molecules, and have designed a screening method for the isolation of active compounds from such libraries. A trypsin inhibitor with a X of 9 pM was found from the screening of a library [97]... 

The first compound isolated was designated L and was reported to have MSH activity and lipolytic activity in rabbits but not in rats. L contained 59 residues with 61u as the N-terminus. Ovine and bovine 8-LPH were Isolated next and found to have essentially the same amino acid composition, mol. wt. and biological activity including low-order adrenocorticotropic activity. A side-fraction from the isolation of ovine 8-LPH yielded which exhibited similar biological activity, but was of lower... 

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