화학공학소재연구정보센터
Biotechnology Progress, Vol.33, No.2, 500-510, 2017
General solutions to decompose heterogeneous compositions using antibody afucosylation as a model system
Methods involving the use of mathematical models of competitive ligandreceptor binding to characterize mixtures of ligands in terms of compositions and properties of the component ligands have been developed. The associated mathematical equations explicitly relate component ligand physical-chemical properties and mole fractions to measurable properties of the mixture including steady state binding activity, 1/K-d,K-apparent or equivalently 1/EC50, and kinetic rate constants k(on,apparent) and k(off,apparent) allowing: (1) component ligand physical property determination and (2) mixture property predictions. Additionally, mathematical equations accounting for combinatorial considerations associated with ligand assembly are used to compute ligand mole fractions. The utility of the methods developed is demonstrated using published experimental ligand-receptor binding data obtained from mixtures of afucosylated antibodies that bind FcRIIIa (CD16a) to: (1) extract component ligand physical property information that has hitherto evaded researchers, (2) predict experimental observations, and (3) provide explanations for unresolved experimental observations. (c) 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:500-510, 2017