RESUMO
Chemical protein synthesis allows the construction of well-defined structural variations and facilitates the development of deeper understanding of protein structure-function relationships and new protein engineering strategies. Herein, we report the chemical synthesis of interleukin-2 (IL-2) variants on a multimilligram scale and the formation of non-natural disulfide mimetics that improve stability against reduction. The synthesis was accomplished by convergent KAHA ligations; the acidic conditions of KAHA ligation proved to be valuable for the solubilization of the hydrophobic segments of IL-2. The bioactivity of the synthetic IL-2 and its analogues were shown to be equipotent to recombinant IL-2 and exhibit improved stability against reducing agents.
Assuntos
Dissulfetos/química , Interleucina-2/química , Interleucina-2/síntese química , Técnicas de Química Sintética , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Estabilidade Proteica , SolubilidadeRESUMO
The enantioselective total synthesis of actinorhodin (1) is described. The synthesis features 1)â dual benzyne reactions en route to the monomer, 2)â the trans-selective installation of the side chain, and 3)â a regioselective oxidative dimerization.