CONVENIENT TOTAL SYNTHESIS OF A 4-HELIX TASP MOLECULE BY CHEMOSELECTIVE LIGATION

The chemoselective ligation approach to the preparation of complex peptides has been used in a simple, convenient synthesis of a template-assembled synthetic protein (TASP) molecule. Reaction of a readily prepared synthetic pro-helical peptide-alphaCOSH, in unprotected form, with a synthetic (BrAc)4 template molecule, also in unprotected form, proceeded rapidly in aqueous solution to give a uniform product in high yield. The resulting 4-helix TASP was simply purified to homogeneity, and the covalent structure was defined by ion-spray mass spectrometry [obs MW 6647.1 +/- 2.8 D; calc 6645.6 (monoisotopic), 6649.9 (average isotope composition)]. The conformation of the resulting macromolecule was determined by circular dichroism (CD) and was highly helical. The chemoselective ligation of unprotected peptides represents a general approach to the synthesis of TASP molecules.