Oligomer Synthesis - Improving on Mother Nature

A host of other oligomer-based scaffolds have been described. Often, the scope and limitations are difficult to gauge, as their use is largely restricted to the academic groups that first devised the methodology. Schultz,for example, has reported on the solid-phase synthesis of oligocarbamates. In one application, a library of 

We described an unusual oligomer whereby a-amino acids were converted into a-hydroxy acids by oxidative deamination with retention of stereochemistry, followed by reduction to 1,2-diols. The primary alcohol was protected by the dimethoxytrityl group, and the remaining secondary alcohol converted to a phos-phitylating agent. These monomers could then be incorporated into oligomers under the standard conditions of automated DNA synthesis. The resulting molecules retain amino acid side-chains, but have the phosphodiester backbone more familiar to nucleic acids. 

It is not always clear if any of the new scaffolds are significantly superior to nature s peptides or nucleotides. Just like the latter, all oligomers inherently suffer from the disadvantage of increasingly likely violation of Lipinski s Rule of Five or other descriptors of drug-like properties as the number of residues in the sequence 

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