Bioactivity data transforming

A standard assumption in QSAR studies is that the models describing the data are linear. It is from this standpoint that transformations are performed on the bioactivities to achieve linearity before construction of the models. The assumption of linearity is made for each case based on theoretical considerations or the examination of scatter plots of experimental values plotted against each predicted value where the relationship between the data points appears to be nonlinear. The transformation of the bioactivity data may be necessary if theoretical considerations specify that the relationship between the two variables... 

Structural information and computational methods have considerable potential in supporting the transformation of bioactive peptides into small molecules. Of major importance is combining all available information on the system of interest, including peptide SAR data, information on the consequences of mutations in the target on SAR, structural information from both the target protein and related proteins as well as the particular ligand and all other known ligands. 

Palinurin. Hamann and co-workers reported the results of an interesting biocatalytic transformation of the furan ring to the corresponding amide in the bioactive marine natural product palinurin (46, X=0). The authors utilized long-range data to... 

We obtained 7-oxoisodrimenin by oxidation of the keto diol (131) with an excess of PCC [92], On oxidation of (131) with Mn02 or PCC (2 mol. equivalents), a mixture of the semiacetals (132) and (133) and keto lactone (136) was obtained. One of these semiacetals, (133) was isolated by crystallization, and its structure and stereochemistry were confirmed by X-ray data [93]. The mixture of semiacetals (132) and (133) was further oxidised to the keto lactone (136). This lactone has no biological activity itself, but it has been used as an intermediate in the total synthesis of bioactive ( )-warburganal (16) [84]. The ethylene ketal (140) of the keto lactone (136) was converted into the keto diol (131), whose transformation to warburganal (16) was discussed above (Scheme 23). 

In each data sheet, the core of information is the identification of substructural modification patterns which could be utilized as possible "rules" for the bioisosteric transformation in the lead evolution phase of the dnig design research not only within a single series, but also extended into other categories of bioactive compounds. There are numerous examples in which the structural evolution has occurred from agrochemicals to medicines (an example is the azole-type antimycotics shown in Fig. 1), from herbicides to fungicides as well as to insecticides and vice versa (Fujita, T. In Trends in QSAR and... 

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