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