Total synthesis of [L40I, C90A, C109A]-human T-cell leukemia virus type 1 protease

[L40I, C90A, C109A]-Human T-cell leukemia virus type 1 protease, which contains 125 amino acid residues, was synthesized by means of the thioester method. The construction of the backbone of this protease involved the synthesis of three building blocks, using the Boc solid-phase method. To suppress epimerization during the first segment coupling between Phe and Arg by the thioester method. DMF was employed as a solvent for the reaction. The amount of D-Phe-containing coupling product in the total product was less than 6% and the desired product was isolated by reverse-phase HPLC in 59% yield. The synthetic product showed enzymatic activities comparable to those reported for the [L40I, C90A, C109A]-human T-cell leukemia virus type 1 protease, prepared by an expression method. (C) 2002 Elsevier Science Ltd. All rights reserved.