SBIR-STTR Award

This innovation is aimed at providing a new methodology for quantitative structure-activity relationships (QSAR) analysis of biopharmaceutical agents. Analysis of quantitative structure-activity relationships is fundamentally important for rational drug design. While QSAR analysis is widely used for common dugs, it is virtually non-existent for various technical reason for biologically active therapeutic agents. ANALIZA is proposing to develop and validate a new methodology for quantitatie measurements of hydrophobic properties useful for QSAR of biopharmaceuticals, such as peptides, proteins, oligonucleotides, etc. The proposed methodology is unique ( in regard to the type of information obtained), quantitative and universal ( in that may be used for comparison of compounds of completely different chemical nature and structure), inexpensive and easy to perform (and thus a viable and cost effective alternative to current structure optimization techniques). Phase I portion of this SBIR program is designed to validate the feasibility of he proposed methodology via a direct demonstration of a QSAR analysis as applied to a series of structurally different peptides and proteins with varied biological activities as provided by biopharmaceutical partners. PROPOSED COMMERCIAL APPLICATION: A new methodology for application of quantitative structure-activity relationship (QSAR) analysis to biological therapeutic agents would improve rational design of chemical modifications beneficial for manufacturing of biological therapeutic agents with improved efficacy, safety, and stability. It should thus provide a new powerful tool for timely advancements in the rapidly growing field of biopharmaceuticals.

Thesaurus Terms:
biological product, chemical structure /function, chemical structure function, drug /agent, drug screening /evaluation, method development acidity /alkalinity, analytical chemistry, drug design /synthesis /production, hydropathy, protein structure /function, protein structure functionNational Institute of General Medical Sciences (NIGMS)

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. PROPOSED COMMERCIAL APPLICATION: 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.