Poly (N-substituted glycines) with nucleotide base substituents

An automated solid-phase method for the synthesis of poly (N-substituted glycines) (referred to herein as poly NSGs) taught here can be used to obtain poly NSGs of potential therapeutic interest which poly NSGs can have a wide variety of side chain substituents. Each N-substituted glycine monomer is assembled from two "sub-monomers" directly on the solid support. Each cycle of monomer addition consists of two steps: (1) acylation of a resin-bound secondary amine with an agent such as a haloacetic acid, and (2) introduction of the side-chain by nucleophilic displacement of the halogen (as a resin-bound alpha-haloacetamide) with an excess of primary amine. The efficient synthesis of a wide variety of oligomeric NSGs using automated synthesis technology, as presented here, makes these polymers attractive candidates for the generation and rapid screening of diverse peptidomimetic libraries. The oligomers of N-substituted glycines (i.e. poly NSGs) disclosed here provide a new class of polymers not found in nature, but which are synthetically accessible and have been shown to possess significant biological activity and proteolytic stability.