Total chemical synthesis of human activin βA[12-116] and related large-loop polypeptides

We report here the synthesis, purification, and characterization of several large polypeptides related to the human activin β_A subunit and their cyclic counterparts. In particular, we describe for the first time the total chemical synthesis of a 105-mer polypeptide, des[1-11] activin β_A, and related large-loop polypeptide, by an optimized solid phase synthetic protocol based on 9-flouroenylmethyoxycarbonyl (Fmoc) chemistry. These studies show that automated chemical synthesis utilizing Fmoc-based solid phase synthetic strategies provides a practical alternative to recombinant DNA technology for the production of activin-related subunits, with the opportunity to rapidly provide different analogues and structural variants for subsequent structure-function and associated biophysical investigations.