Method for preventing deletion sequences in solid phase synthesis

Improved methods for solid-state synthesis of polymers, especially polypeptides and polynucleotides, are provided. In accordance with a preferred embodiment, selectively activatable and reactive bonding moieties are covalently bonded to solid supports for polynucleotide and polypeptide syntheses. Products of failed reactions and some side products are caused to react with the selectively activatable and reactive bonding moiety to cause divalent bonding of unwanted products to the solid support. Upon cleavage of the initial situs of covalent bonding to the solid support, desired products are free to be collected while unwanted products remain covalently bonded to the support. Ease of purification of such polymers is a principal object of the present invention. The methods of the invention are amenable to automation and digital control and novel solid supports, activatable, reactive bonding moieties and other compositions are presented. The expression of polynucleotides prepared in accordance with preferred embodiments produces novel polypeptides.