POLYETHYLENE GLYCOL ADDITION TO RECOMBINANT PROTEINS

The long range objective of this proposal is to find mild, highly specific conditions for the targeted addition of polyethylene glycol to specific residues of recombinant proteins. Because proteins which have been modified by polyethylene glycol addition have increased serum persistence and decreased immunogenicity, this objective, if achieved, has the potential to decrease the frequency of parenteral administration of recombinant proteins, and may allow larger and more complex biological structures, such as viruses of cells, to be modified so as to increase their biological half life and decrease the rate at which they are removed or destroyed by the immune system. Much of the work proposed is aimed at obtaining precise information about the behavior of small model compounds which mimic the polyethylene glycol substituents intended for ultimate use. $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 342 --PROJECT NUMBER......1 R43 GM56061-01 INVESTIGATOR NAME/ADDRESS FY 97 ZASLAVSKY, BORIS Y IRG/INTRAMURAL UNIT..ZRG3 ANALIZA INC AWARD AMOUNT......... $94,588 408 GLEN PARK DRIVE BAY VILLAGE OH 44140 PERFORMING ORGANIZATION: ANALIZA, INC. TITLE NEW METHOD FOR QSAR FOR BIOPHARMACEUTICAL PRODUCTS ABSTRACT: 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.