Improving the species cross-reactivity of an antibody using computational design. Export

@article{citeulike:6080392, abstract = {The high degree of specificity displayed by antibodies often results in varying potencies against antigen orthologs, which can affect the efficacy of these molecules in different animal models of disease. We have used a computational design strategy to improve the species cross-reactivity of an antibody-based inhibitor of the cancer-associated serine protease MT-SP1. In silico predictions were tested in vitro, and the most effective mutation, T98R, was shown to improve antibody affinity for the mouse ortholog of the enzyme 14-fold, resulting in an inhibitor with a K(I) of 340 pM. This improved affinity will be valuable when exploring the role of MT-SP1 in mouse models of cancer, and the strategy outlined here could be useful in fine-tuning antibody specificity.}, author = {Farady, Christopher J. and Sellers, Benjamin D. and Jacobson, Matthew P. and Craik, Charles S.}, citeulike-article-id = {6080392}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.bmcl.2009.05.005}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19477127}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19477127}, day = {15}, doi = {10.1016/j.bmcl.2009.05.005}, issn = {1464-3405}, journal = {Bioorganic \& medicinal chemistry letters}, keywords = {computational, design}, month = {July}, number = {14}, pages = {3744--3747}, posted-at = {2009-11-06 10:24:23}, priority = {2}, title = {Improving the species cross-reactivity of an antibody using computational design.}, url = {http://dx.doi.org/10.1016/j.bmcl.2009.05.005}, volume = {19}, year = {2009} }

TY - JOUR ID - citeulike:6080392 L3 - citeulike-article-id:6080392 N2 - The high degree of specificity displayed by antibodies often results in varying potencies against antigen orthologs, which can affect the efficacy of these molecules in different animal models of disease. We have used a computational design strategy to improve the species cross-reactivity of an antibody-based inhibitor of the cancer-associated serine protease MT-SP1. In silico predictions were tested in vitro, and the most effective mutation, T98R, was shown to improve antibody affinity for the mouse ortholog of the enzyme 14-fold, resulting in an inhibitor with a K(I) of 340 pM. This improved affinity will be valuable when exploring the role of MT-SP1 in mouse models of cancer, and the strategy outlined here could be useful in fine-tuning antibody specificity. IS - 14 JF - Bioorganic & medicinal chemistry letters SN - 1464-3405 EP - 3747 TI - Improving the species cross-reactivity of an antibody using computational design. VL - 19 SP - 3744 KW - computational KW - design AU - Farady, Christopher AU - Sellers, Benjamin AU - Jacobson, Matthew AU - Craik, Charles PY - 2009/07/15/ UR - http://dx.doi.org/10.1016/j.bmcl.2009.05.005 ER -