| Literature DB >> 24949974 |
Erik Procko1, Geoffrey Y Berguig2, Betty W Shen3, Yifan Song1, Shani Frayo3, Anthony J Convertine2, Daciana Margineantu3, Garrett Booth3, Bruno E Correia4, Yuanhua Cheng2, William R Schief4, David M Hockenbery3, Oliver W Press3, Barry L Stoddard3, Patrick S Stayton2, David Baker1,5.
Abstract
Because apoptosis of infected cells can limit virus production and spread, some viruses have co-opted prosurvival genes from the host. This includes the Epstein-Barr virus (EBV) gene BHRF1, a homolog of human Bcl-2 proteins that block apoptosis and are associated with cancer. Computational design and experimental optimization were used to generate a novel protein called BINDI that binds BHRF1 with picomolar affinity. BINDI recognizes the hydrophobic cleft of BHRF1 in a manner similar to other Bcl-2 protein interactions but makes many additional contacts to achieve exceptional affinity and specificity. BINDI induces apoptosis in EBV-infected cancer lines, and when delivered with an antibody-targeted intracellular delivery carrier, BINDI suppressed tumor growth and extended survival in a xenograft disease model of EBV-positive human lymphoma. High-specificity-designed proteins that selectively kill target cells may provide an advantage over the toxic compounds used in current generation antibody-drug conjugates.Entities:
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Year: 2014 PMID： 24949974 PMCID： PMC4079535 DOI： 10.1016/j.cell.2014.04.034
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582