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Metabolic detrimental transformation

The replacement of a nitrile with a carboxylic acid group is the least detrimental transformation, and is an example of an atypical bioisosteric replacement. Moreover, there are a few others that add polarity to the molecule, such as methyl to methyl amide, addition of a isobutyric acid, 1,2-phenyl to 2,3-pyridine, and 2,3-pyridine to 2,3-pyrazine groups. Interestingly, the substitution of a methyl with an exotic trifluoromethyl ether moiety [34] is bioisosteric, even though there is a considerable increase in lipophilidty. This is also the case for the replacement of the more metabolically labile isopropyl ether with the cydopropyl group. Finally, a little considered bioisosteric transformation is 2-thiophene to para-fluorophenyl, which has been very recently proposed in a large-scale MMP analysis [35]. [Pg.118]

Identification of the overall neutral, least detrimental, and least favorable transformations with regard to metabolic stability and identification of interesting isosteres. [Pg.113]

One may relax the definition of bioisosteres and also include transformations that either maintain or improve metabolic stability. To that end. Table 6.5 lists the 10 least detrimental (top) as well as the 10 least favorable (bottom) transformations in terms of metabolic stability. With regard to the latter, the 10 least favorable transformations can be converted to favorable ones, by reversing the direction of the transformation listed in the table. [Pg.118]

Table 6.5 The 10 least detrimental (top) and the 10 least be neficia 1 (bottom) transformations found for metabol ic stability. ... [Pg.119]

Unless the appropriate inhibitory treatments are applied, lactic acid bacteria are part of the normal microflora of aU white and red wines. From the start to the end of fermentation, and even during aging and storage, they alternate between successive growth and regression periods depending on the species and the strains. AU multiplication or survival involves a metabolism that is perhaps very active or, on the contrary, hardly perceptible and even impossible to detect with current analytical methods. Substrates are transformed and consequently organoleptic characters are modified. Some metabolic activities are favorable and others are without consequence, whUe some are totally detrimental to wine quaUty (Volume 2, Section 8.3). [Pg.157]

A synthetic operon (the ace4 operon) composed of four C. acetobutylicum ATCC 824 genes adc, ctfA, ctfB, and thl) under the control of the thl promoter was constructed to allow E. coli to produce acetone (Bermejo et al. 1998). The thiolase gene (thl) is included for the conversion of acetyl-Co A to acetoacetyl-CoA (see the section O Metabolic Pathways and Enzymology of Solvent Production in this chapter). One of the transformed E. coli strains, ATCC 11303 (pACT), produced 125-154 mM of acetone when sodium acetate was added to glucose-fed cultures. Besides their potential usefulness for acetone production, it was suggested that the recombinant strains may be useful hosts for recombinant protein production in that detrimental acetate accumulation can be avoided (Bermejo etal. 1998). [Pg.104]


See other pages where Metabolic detrimental transformation is mentioned: [Pg.1933]    [Pg.397]    [Pg.921]    [Pg.279]    [Pg.157]    [Pg.1392]    [Pg.456]    [Pg.437]    [Pg.513]    [Pg.109]    [Pg.179]    [Pg.166]   
See also in sourсe #XX -- [ Pg.119 ]




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