Abstract
Statistical experimental design provides an efficient approach for selecting the building blocks to span the structural space and increase the information content in a combinatorial library. A set of renin-inhibitors, hexapeptoids, is used to illustrate the approach. Multivariate quantitative structure-activity relationships (MQSARs) were developed relating renin inhibition to the peptoid sequences variation, parametrized by the z-scales. By using the information from the models, the number of building block sets could be reduced from six to three. Using a statistical molecular design (SMD) reduces the number of compounds from more than 100 000 down to 90. A second SMD was used for comparison, based on less prior knowledge. This gave a reduction from over 2 billion to 120 compounds.
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Linusson, A., Wold, S. & Nordén, B. Statistical molecular design of peptoid libraries. Mol Divers 4, 103–114 (1998). https://doi.org/10.1023/A:1026416430656
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DOI: https://doi.org/10.1023/A:1026416430656