It is estimated that about 800 non-proteinogenic amino acids (NPAAs) have been identified in bacteria, fungi, plants and marine organisms, leaving the 20 proteinogenic amino acids in the minority at 4%. The existence of many hundreds of biologically active natural peptides with one or more NPAAs, reflects the ability of these particular monomers to confer some useful functional properties, not available in the basic set of 20 amino acids. The incorporation of NPAAs into peptides leads to modifications in the secondary structure that often result in improved selectivity, bioavailability, and stability. Moreover, they are extensively used in the synthesis of peptide catalysts, and functional materials. Finally, NPAAs are versatile intermediates in organic synthesis, especially in drug discovery. The broad utility of NPAAs therefore makes them one of the most important classes of organic molecules.
C-glycosyl α-amino acids
C-Glycosyl amino acids are a group of C-glycosides in which a carbohydrate molecule is attached to the side chain or backbone of the amino acid via a C–C bond. We obtained C-glycosyl α-amino acids by modification of the Passerini products, and presented a protocol for the synthesis of oligomers containing alternating C-glycosyl α-amino acids and proteinogenic α-amino acids.
New J. Chem 2024, 48, 12584 - 12590.
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A versatile synthetic approach employing customised C-glycosyl α-amino acids enables the preparation of C-glycopeptides with precise spatial incorporation of non-canonical residues. NMR analyses reveal that the identity, number, and distribution of C-glycosyl units govern peptide conformations via intramolecular hydrogen bonding between backbone amides and carbohydrate side chains.
Angew. Chem. Int. Ed. 2025, DOI: 10.1002/anie.202522704
α-Hydrazino acids
We demonstrated possibility to finely modulate peptide interactions with DNA/RNA by α-hydrazino group insertion and showed how the different positioning of two α-hydrazino groups in peptides controls binding to various double stranded and single stranded DNA and RNA, whereby the binding mode is a combination of electrostatic interactions and hydrophobic interactions within DNA/RNA grooves.​ ​
Org. Biomol. Chem. 2016, 14 ,4865–4874
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Based on NMR data, we report structural models of p53-derived hydrazino peptides with elements of localized peptide structuring in the form of an α-, β-, or γ-turn as a result of hydrazino modification in the peptide backbone. The modifications could potentially lead to the preorganization of a helical secondary peptide structure in a solution that is favorable for binding to a biological receptor.
ACS Omega, 2024, 20, 22175-22185
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A structurally diverse library of chiral Nβ- substituted 1,2-diazetidin-3-ones was obtained by a 4-center 3-component Ugi reaction comprising unprotected α-hydrazino acids.
J. Org. Chem. 2022, 87, 7076−7084
