Synthesis and Conformational Analysis of Aminopyrazolonyl Amino Acid (APA)/Peptides

Abstract

Pyrazole, pyrazolone, and aminopyrazolone derived molecules are bioactive molecules and considered as potential therapeutic drug candidates because of their unique structural properties. These molecules have abilities to interact with several bio‐macromolecules via non‐covalent interactions such as hydrogen bonding and π–π interactions. In structural organization of dipeptides, pyrazole containing aromatic amino acid/dipeptides have been explored and considered as potential amino acid residue. In repertoire of unnatural aromatic amino acids, this report describes the synthesis of 4‐aminopyrazolonyl containing amino acids and their crystal structures. The incorporation of 4‐aminopyrazolonyl at N‐terminal of native amino acid/dipeptides influences the conformational changes of respective peptide which induces the formation of distinctive supramolecular self‐assembly structures such as β‐sheet and α‐helices in their solid‐state crystal. The structural conformation of those peptides, here, are also demonstrated in solution phase by 1H‐NMR (1D/2D) and [D6]DMSO titration methods which support the formation of inter‐/intramolecular hydrogen bonding in solution. Hence, these unnatural amino acid analogues can tune the secondary structure of natural amino acid/peptides by introducing at N‐terminal via amide bond.