Improving Biologic Drugs via Total Chemical Synthesis

Date:2016-03-29 12:48:00

Most biologic therapeutics are large, complex molecules or heterogeneous mixtures of molecules that are manufactured in a living system (e.g., microorganism, plant cell, or animal cell) through recombinant DNA technology. Biologics are now being used to treat a wide range of diseases, including cancer, autoimmune disorders, and diabetes. It is estimated that half of the top 100 best-selling medications will soon be biologics, with Roche's anticancer biologic Avastin and AbbVie's anti-inflammatory antibody Humira rivaling the success of Pfizer's small-molecule drug Lipitor (1). Biologics differ fundamentally from small-molecule drugs in terms of purity, composition, and production. Small-molecule drugs typically have homogeneous, well-defined structures that have been finely tuned with atomic-level precision via chemical synthesis. On page 1357 of this issue, Wanget al. (2) bridge the gap between biologics and small-molecule drugs by accomplishing the total chemical synthesis of the biologic erythropoietin (EPO) in a single, pure form.

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