Bioactivity data scaling

Muresan S, Petrov P, Southan C, et al. Making every SAR point count The development of chemistry connect for the large-scale integration of structure and bioactivity data. Drug Discov Today 2011 16 1019-1030. 

Inflammation is associated with various diseases such as rheumatoid arthritis, cancer, myocarditis, arteriosclerosis, bowel diseases, multiple sclerosis, asthma, and many others. While several inflammatory markers are commonly expressed during any inflammatory disorder, some are symptom specific. Therefore, the gene array data will be particularly helpful in indicating the appropriate disease model for subsequent preclinical and clinical tests. Only functional, active extracts with potentially safe and novel modes of actions may then be subjected to labor-intensive large-scale extraction, fractionation, characterization, and isolation of novel bioactive components. We believe that the strategy as described schematically in Figure 4.1 will allow efficient use of plant extracts and other natural resources toward identification of novel drug leads for human health care. 

Conformational analyses of JOM-13 and [L-Ala3]DPDPE have proven to be critical for the determination of the bioactive conformation of enkephalin-like peptides at the delta receptor. H-NMR studies of JOM-13 in aqueous solution revealed that this tetrapeptide exists in two distinct conformations on the NMR time scale as evidenced by two sets of resonances [63]. Large differences in the observed chemical shifts and coupling constants for the D-Cys2 residue in the two conformers suggested that the major differences between the two NMR conformers reside in the disulfide portion of the molecule however, a paucity of conformationally informative nuclear Overhauser enhancement (NOE) interactions precluded the development of a detailed structural model from the NMR studies. In order to develop such a model a thorough conformational analysis of JOM-13 was undertaken, in which the NMR data were complemented by x-ray diffraction results and by molecular mechanics calculations [64]. The results indicate that the 11-... 

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