Peptidomimetics are compounds whose essential elements (pharmacophore) mimic a natural peptide or protein in 3D space and which retain the ability to interact with the biological target and produce the same biological effect. The demand for modified peptides with improved stability profiles and pharmacokinetic properties is driving extensive research effort in this field. Many structural modifications of peptides guided by rational design and molecular modeling have been established to develop novel synthetic approaches. A significant impact of structure-based drug design has emerged over recent years in the discovery of novel peptidomimetics and nonpeptides. Such reesearch has been catalyzed by X-ray crystallography and NMR spectroscopy as well as computational chemistry methodologies. Many drugs that we use are proteinic in nature,
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Classification of peptidomimetics:
A new classification of peptidomimetics based on the degree of their similarity to the natural peptide precursor, thereby resulting in four different classes A–D, where A features the most and D the least similarities. Classes A and B include peptide-like structures (differentiating type I and partially including type III mimetics) whereas classes C and D encompass small molecular scaffolds (including type II and to some extent type III mimetics):
• Class A mimetics are defined as peptides that mainly consist of the parent peptide amino acid sequence. Only a limited number of modified amino acids are introduced to stabilize the bioactive conformation. The backbone and side chains of a class A mimetic align closely with the bioactive conformation of the precursor peptide.
• Class B involves further modified class A mimetics with various non-natural amino acids, isolated small-molecule building blocks, and/or major backbone alterations. This class also includes foldamers, such as β- and α/β-peptides as well as peptoids, which align their side chains topologically similar to the precursor
Classification of peptidomimetics:
A new classification of peptidomimetics based on the degree of their similarity to the natural peptide precursor, thereby resulting in four different classes A–D, where A features the most and D the least similarities. Classes A and B include peptide-like structures (differentiating type I and partially including type III mimetics) whereas classes C and D encompass small molecular scaffolds (including type II and to some extent type III mimetics):
• Class A mimetics are defined as peptides that mainly consist of the parent peptide amino acid sequence. Only a limited number of modified amino acids are introduced to stabilize the bioactive conformation. The backbone and side chains of a class A mimetic align closely with the bioactive conformation of the precursor peptide.
• Class B involves further modified class A mimetics with various non-natural amino acids, isolated small-molecule building blocks, and/or major backbone alterations. This class also includes foldamers, such as β- and α/β-peptides as well as peptoids, which align their side chains topologically similar to the precursor