Physical instability of a therapeutic Fc fusion protein: domain contributions to conformational and colloidal stability.

Protein therapeutics made up of artificially combined proteins or protein domains, so-called fusion proteins, are a novel and growing class of biopharmaceuticals. We have studied abatacept (Orencia), a fusion protein that is constructed of a modified IgG Fc domain and the soluble part of the T-cell receptor CTLA-4. In accelerated degradation studies conducted at 40 degrees C, a pH shift from 7.

Deciphering the mechanism of thermodynamic accommodation of telomeric oligonucleotide sequences by the Schizosaccharomyces pombe protection of telomeres 1 (Pot1pN) protein.

Linear chromosomes terminate in specialized nucleoprotein structures called telomeres, which are required for genomic stability and cellular proliferation. Telomeres end in an unusual 3' single-strand overhang that requires a special capping mechanism to prevent inappropriate recognition by the DNA damage machinery. In Schizosaccharomyces pombe, this protective function is mediated by the Pot1 protein, which binds specifically and with high affinity to telomeric ssDNA.