FACILE SYNTHESIS OF HOMOGENEOUS ARTIFICIAL PROTEINS

A new approach, involving oxime formation, is described for the synthesis of stable macromolecules of defined structure and is exemplified with polypeptides. In a first step, purified polypeptide fragments, carrying either aldehyde or aminooxy groups but devoid of protecting groups, are prepared. In a second step, these fragments spontaneously self-assemble on an appropriate synthetic template under very mild conditions through formation of oxime bonds. The resulting oximes are stable in water at room temperature at pH 2-7. One of the compounds made, the covalent structure of which was defined by electrospray mass spectrometry [observed MW 19 916.61 +/- 3.05 D; calculated MW 19 916.10 (average isotopic composition)], would seem to be the largest artificial protein ever made, in pure form in good yield, by controlled total synthesis. Possible applications of this method of synthesis of homogeneous macromolecules include vaccines, biosensors, and enhanced peptide libraries.