Macrocyclization strategies for cyclic peptides and peptidomimetics
| Autor: | Christina Lamers, Clément Bechtler |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Pharmacology
chemistry.chemical_classification Flexibility (engineering) 010405 organic chemistry Peptidomimetic Computer science Organic Chemistry Pharmaceutical Science Peptide 010402 general chemistry 01 natural sciences Biochemistry Combinatorial chemistry Cyclic peptide 0104 chemical sciences 3. Good health Chemistry chemistry Drug Discovery Screening method Peptide chemistry Molecular Medicine |
| Zdroj: | RSC Medicinal Chemistry |
| ISSN: | 2632-8682 |
| Popis: | Peptides are a growing therapeutic class due to their unique spatial characteristics that can target traditionally “undruggable” protein–protein interactions and surfaces. Despite their advantages, peptides must overcome several key shortcomings to be considered as drug leads, including their high conformational flexibility and susceptibility to proteolytic cleavage. As a general approach for overcoming these challenges, macrocyclization of a linear peptide can usually improve these characteristics. Their synthetic accessibility makes peptide macrocycles very attractive, though traditional synthetic methods for macrocyclization can be challenging for peptides, especially for head-to-tail cyclization. This review provides an updated summary of the available macrocyclization chemistries, such as traditional lactam formation, azide–alkyne cycloadditions, ring-closing metathesis as well as unconventional cyclization reactions, and it is structured according to the obtained functional groups. Keeping peptide chemistry and screening in mind, the focus is given to reactions applicable in solution, on solid supports, and compatible with contemporary screening methods. Macrocyclization between head, tail or sidechains is a frequently employed strategy to enhance peptide and peptidomimetic stability, selectivity and affinity. |
| Databáze: | OpenAIRE |
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