Recent developments in the utility of saturated azaheterocycles in peptidomimetics

Abstract

To large extent, the physical and chemical properties of peptidomimetic molecules are dictated by the integrated heterocyclic scaffolds they contain. Heterocyclic moieties are introduced into a majority of peptide-mimicking molecules...

Stereoselective synthesis of (R)- and (S)-1,2-diazetidine-3-carboxylic acid derivatives for peptidomimetics

“…Therefore, they have been widely applied in peptidomimetics where they can act as Pro surrogates to modulate the conformational flexibility, bioavailability, proteolytic stability and biological activity of target molecules. 4 The six-membered cyclic α-hydrazino acid (n = 3), known as piperazic acid (Pip), is a non-proteinogenic amino acid and the only example of a naturally occurring member of this family (Fig. 1).…”

“…Therefore, they have been widely applied in peptidomimetics where they can act as Pro surrogates to modulate the conformational flexibility, bioavailability, proteolytic stability and biological activity of target molecules. 4…”

Biocatalytic Synthesis of l‐Pipecolic Acid by a Lysine Cyclodeaminase: Batch and Flow Reactors

“…Moreover, the biosynthetic approaches allow for the use of the low-cost l-Lysine as a starting material, thus increasing the value of the final drug. [3] Typically, l-PA synthesis has been performed using chemical methods that involve harsh conditions and hazardous reagents, mainly due to the difficulty of obtaining optically pure l-PA. [4][5][6] In the last fifty years, several multi-step syntheses including protection-deprotection steps and using organic solvents yielded ~45 % of Pipecolic Acid starting from l-Lysine. [7][8][9] In 2021, a highly selective method has been developed by starting with Oppolzer chiral sultam and yielding 81 % of Pipecolic Acid.…”

A Non‐coded β2,2‐Amino Acid with Isoxazoline Core Able to Stabilize Peptides Folding through an Unprecedented Hydrogen Bond

“…[16] Indeed, having more stable bioactive conformation in comparison with natural peptides, peptidomimetics are considered interesting candidates for modulations of protein-protein interactions modulations. [17] The use of α,α-disubstituted AAs or β-homologues of natural amino acids have been extensively studied to stabilize peptide conformation. [8,18,19] On the other hand, few examples of the more complex and not easily accessible β 2,2 -AAs are reported in literature, [20][21][22][23][24] giving interesting stable conformations.…”

“…For this reason, the preparation of peptidomimetics is a promising strategy for the obtainment of next‐generation therapeutics [16] . Indeed, having more stable bioactive conformation in comparison with natural peptides, peptidomimetics are considered interesting candidates for modulations of protein‐protein interactions modulations [17] …”