Biological stabilization

Biological stability Very good Very good Very good Very good... 

The D- -)-o -aminobenzylpenicillin may then be recovered from the aqueous reaction mixture by concentration to small volume and recovering the product by filtration. However, due to the fact that anhydrous D- -)-a-aminobenzylpenicillin is soluble in water to the extent of about 20-25 mg/ml at 20°-25°C, it is very difficult to recover the product in high yields. Furthermore, the recovered D- -)-a-aminobenzylpenicillin may be obtained in the form of a monohydrate. The monohydrates as well as the dihydrates) of D- -)-a-amino-benzylpenicillin possess poor biological stability. 

The trihydrate which is obtained in high yields, is relatively insoluble in water, possesses high biological stability and can be obtained by contacting, at a temperature not above 60°C, an acid addition salt of D-(-)-a-aminobenzylpenicillin with an amine in a water-immiscible solvent containing at least 3 mols of water per mol of such penicillin. 

GL17 Stability Biotechnologicals/ biologicals Stability testing of new biotechnological/bio-logical products... 

Desmopressin. Desmopressin is an analogue to the endogenous antidiuretic peptide hormone Vasopressin in which the modifications of the N-terminous amino acid and the replacement of the L-Arg for a D-Arg in position 8, significantly increases its biological stability. In this investigation, the half-life of dDAVP in the rabbit after intravenous administration was determined to be approximately 45 minutes. 

Somatostatin. Somatostatin is an endogenous peptide hormone involved in e.g. the control of the release of Somatomedin, Insulin and Pancreatin. Due to its biological role, Somatostatin has a very low biological stability. The half-life in the rabbit after intravenous administration has been determined to approximately 90 seconds in this investigation. After sc or im administration, the apparent half-life is somewhat longer, close to 10 minutes, probably due to the absorption of the peptide from the injection site into the systemic circulation. 

Albumin. Albumin is available in highly pure and uniform form, and exhibits low toxicity and good biological stability. It has been used as a carrier for methotrexate and a variety of antiviral drugs [amantadine, fioxuridine (5-fluorodeoxyuridine), and cytar-abine (cytosine arabinoside)] to treat macrophage tumors and infections caused by DNA viruses growing in macrophages. Heavily modified albumins are known... 

Azmi W, Banerjee UC (2002) Biological stabilization of textile and dye stuff industrial waste. Indian Chem Eng Sec A 44 230-234... 

Owing to their chemical, physical and biological stability, PCDD/PCDFs are able to remain in the environment for a long time. As a consequence, dioxins from so-called primary sources (formed in industrial or combustion processes) are transferred to... 

WILLIAMS, A.G., SHAW, M. and ADAMS, S.J. (1984). The biological stability of aerobically-treated piggery slurry during storage. J. agric. EngngRes. 29,231-239... 

Many observations document that modifications of peptides by substitution with artificial amino acids or D-amino acids can often protect against enzymatic degradation. This is especially true when more than one modification is made. We begin here with two examples in which replacement of a single natural amino acid with an artificial one had a favorable impact on biological stability. Then, the influence of substitution with D-amino acids is described. Examples involving two or more modifications with artificial amino acids and D-amino acids combined are presented in the following section. 

Much has been published on the design, synthesis, and activities of pep-toids, pseudopeptides, and peptidomimetics. In contrast, published reports on their biological stability, metabolism, and pharmacokinetics are scarce, making it currently impossible to draw robust conclusions or even to delineate sound trends. This is an unfortunate situation given the vast amount of data that remains buried in industrial archives. 

D. Brewster, M. J. Ranee, An Analogue of Thyrotropin Releasing Hormone with Improved Biological Stability Both in vitro and in vivo, Biochem. Pharmacol. 1980, 29, 2619-2623. 

J. Frackenpohl, P. I. Arvidsson, J. V. Schreiber, D. Seebach, The Outstanding Biological Stability of ]3- and y-Peptides toward Proteolytic Enzymes An in vitro Investigation with Fifteen Peptidases , ChemBioChem 2001, 2, 445-455. 

A- [(Acy loxy )methyl] derivatization was also examined for its potential to improve the biological stability of peptides. For example, the peptide-like model A-[(benzyloxy )carbonyl]glycine benzylamide (8.171, R = H) was de-rivatized to a few N-/Yacyloxy)methyl] derivatives whose chemical and enzymatic hydrolysis was investigated [225], The results compiled in Table 8.13 indicate a fast chemical hydrolysis, the mechanism of which is depicted as Reaction b in Fig. 8.21. Enzymatic hydrolysis also occurs in human plasma, resulting in short half-lives, with the exception of the pivaloyl analogue. 

Chemical and biological stability in aquarium systems. J. Agric. Food Chem., 15(1) 148-156,1967. 

Frechet and coworkers have popularized poly(aryl ether) dendrimers and polyester dendrimers (Fig. 13.7), which have been widely used (Hawker and Frechet 1990 Dire et al. 1998). Addition of the aromatic rings adds rigidity to the dendiimer framework that is lacking in the PPI and PAMAM dendrimers. The polyester dendrimers may be more like the PPIs and PAMAMs in terms of rigidity, but the ester linkages enable degradation of the polyester dendrimers by esterases in vivo. Thus, the biological stability of the PAMAMs and the polyester frameworks is quite different. 

If the pH dependency of biological stability and/or activity is known, a cation exchanger is recommended if this stability is below the pi. 

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