We propose to develop a new methodology for measurement of hydrophobic properties of therapeutic agents. This information is important for Quantitative Structure-Activity Relationships (QSAR) analyses. While the QSAR analysis is widely used for common drugs, it is virtually non-existent for various technical reasons for biological agents. The new methodology should provide information useful for QSAR of bio pharmaceuticals as well as for small compounds. The technique is based on a novel analytical application of partitioning in aqueous polymer two- phase systems. The methodology is unique (regarding the type of information obtained). quantitative and universal (may be used for comparison of compounds of different chemical nature), inexpensive and easy to perform. It thus provides a viable option for obtaining relevant structure-related information during screening early in the discovery process. The principal objective of the Phase II portion is to further develop and validate the technology for a wide variety of biotherapeutical agents, with specific emphasis on peptides, and for common drugs. Additional objectives include evaluation of the technique for analysis of various structural modifications, development of recommended systems and assay conditions, examination of technical issues related to screening applications, development of an automated measurement workstation. and incorporation of the data into modern QSAR techniques.
New relevant information useful for Quantitative Structure-Activity Relationships (QSAR) analysis of therapeutic agents should help improve the rational drug design process. A fast and inexpensive evaluation of an important structure-related descriptor as proposed should help the design of biopharmaceuticals and common drugs of improved efficacy and safety.
|Gulyaeva, Nellie; Zaslavsky, Alexander; Lechner, Pamela et al. (2002) Relative hydrophobicity and lipophilicity of beta-blockers and related compounds as measured by aqueous two-phase partitioning, octanol-buffer partitioning, and HPLC. Eur J Pharm Sci 17:81-93|