Log D versus HPLC derived hydrophobicity: The development of predictive tools to aid in the rational design of
H L Bolt1, C E J Williams2, R V Brooks2
1Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, United Kingdom.
Abstract:
Hydrophobicity has proven to be an extremely useful parameter in small molecule drug discovery programmes given that it can be used as a predictive tool to enable rational design. For larger molecules, including peptoids, where folding is possible, the situation is more complicated and the average hydrophobicity (as determined by RP-HPLC retention time) may not always provide an effective predictive tool for rational design. Herein, we report the first ever application of partitioning experiments to determine the log D values for a series of peptoids. By comparing log D and average hydrophobicities we highlight the potential advantage of employing the former as a predictive tool in the rational design of biologically active peptoids.
