Peptoids are an exciting class of peptidomimetic materials demonstrated to have promising bio-medical applications. The primary difference between peptides and common peptoids (N-alkylated polyglycine) lies in their side-chain position. While in peptides the functional group is positioned on the C<sub>α</sub>, in peptoids it is positioned on the NH. This isomeric difference is reflected in the absence or presence of chirality and rigidity of the oligomeric chain. Secondary structural motifs are mainly results of the side-chain’s chemical nature, the chiral centers, and the level of cis/trans tendency around the amide bonds. The biological activity of the oligomers is eventually affected by these constraints. Two major challenges in the peptoid field are their lack of main-chain chirality and their lack of rigidity arising from their non-fixed cis/trans configuration. These structural characteristics often prevent peptoids from adopting a stable secondary structure, thereby lowering their potential for specific targeting in biological systems. In order to overcome this challenge we are developing densely N-Alkylated Peptide (DNAP) oligomers which are based on doubly substituted monomers (alkylation on both C<sub>α</sub> and NH positions). In addition, starting from common chiral building blocks and Fmoc protection strategies allows main-chain chirality to be maintained while simultaneously enhancing rigidity, features which common peptoids often lack. We will present the synthesis and rigidity/secondary structure studies using EPR (Electron Paramagnetic Resonance) and CD (Circular Dichroism) measurements of this interesting class of materials.

Densely N-alkylated peptides: Unexplored rigid and chiral peptoids

251st National Meeting (2016)

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