Non-Canonical Amino Acids as Building Blocks for Peptidomimetics: Structure, Function, and Applications

Abstract

This review provides a fresh overview of non-canonical amino acids and their applications in the design of peptidomimetics. Non-canonical amino acids appear widely distributed in nature and are known to enhance the stability of specific secondary structures and/or biological function. Contrary to the ubiquitous DNA-encoded amino acids, the structure and function of these residues are not fully understood. Here, results from experimental and molecular modelling approaches are gathered to classify several classes of non-canonical amino acids according to their ability to induce specific secondary structures yielding different biological functions and improved stability. Regarding side-chain modifications, symmetrical and asymmetrical α,α-dialkyl glycines, Cα to Cα cyclized amino acids, proline analogues, β-substituted amino acids, and α,β-dehydro amino acids are some of the non-canonical representatives addressed. Backbone modifications were also examined, especially those that result in retro-inverso peptidomimetics and depsipeptides. All this knowledge has an important application in the field of peptidomimetics, which is in continuous progress and promises to deliver new biologically active molecules and new materials in the near future.

Seaweed Proteins: A Step towards Sustainability?

“…Non-essential amino acids are those that can be synthesized by the body in adequate quantities to meet its needs [ 74 ]. Amino acids have various physiological functions, including regulation of food intake, gene expression, protein phosphorylation, and cell-to-cell communication.…”

Engineered Proteins and Materials Utilizing Residue-Specific Noncanonical Amino Acid Incorporation

“…Amino acids are the building blocks of proteins, and they allow for endless combinations, forming distinct domains within proteins that govern their structure, function, and stability. , The standard genetic code gives rise to 20 amino acids, popularly referred to as the canonical amino acids (cAAs), which are incorporated into proteins biosynthetically during translation. All 20 amino acids share a common backbone () containing a carboxyl and amino group involved in subsequent protein peptide bonding, and they can be grouped based on their variable side chains (Figure ).…”

Morpholine Scaffolds’ Preparation for Foldamers’ Design and Construction

“…It is worth of note that 2morpholine acetals bearing a carboxylic residue, as well as morpholine carboxylic acids, have found wide applications in the synthesis of peptidomimetics as stabilizers or inductors of specific conformations and turns. [34] Concerning morpholine carboxylic acids, an interesting synthetic approach was reported by Penso research group (Scheme 13). [35] The ring-opening of optically pure oxiranes by threonine under solid-liquid phase transfer catalysis (SL-PTC) conditions furnished the diol derivative 30.…”