Cyclic Peptide Synthesis and Biological Activity Evaluations
Summary
Cyclic peptides represent a versatile class of macrocyclic compounds formed by head-to-tail cyclisation of linear amino acid sequences or by incorporation of non-proteinogenic residues. Advances in chemical and enzymatic methodologies have enabled precise control of ring size, stereochemistry and functionalisation, leading to scaffolds with enhanced proteolytic stability, conformational constraint and membrane permeability. Synthetic strategies range from solid-phase peptide synthesis with on-resin macrolactamisation to chemoenzymatic approaches employing nonribosomal peptide synthetases, each affording access to diverse cyclic architectures. Parallel developments in high-throughput screening, molecular docking and cell-based assays have facilitated systematic evaluation of antimicrobial, anticancer, immunosuppressive and enzyme-inhibitory activities. Structure–activity relationships reveal that ring rigidity and side-chain modifications govern target affinity, while incorporation of heterocyclic or fluorinated residues can improve pharmacokinetic properties. Global research efforts now focus on streamlining synthetic workflows, exploiting biosynthetic gene clusters and leveraging computational design to accelerate lead discovery and optimise therapeutic profiles.
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Cyclic Peptide Synthesis and Biological Activity Evaluations publication trend
The graph below shows the total number of articles in cyclic peptide synthesis and biological activity evaluations across all publications each year (not limited to Nature Index journals).
Technical terms
Cyclic peptide: A peptide in which the N-terminus and C-terminus are covalently linked to form a ring, conferring conformational stability and resistance to proteolysis.
Macrocyclisation: The chemical or enzymatic process of forming a large cyclic structure from a linear precursor, typically via amide or ester bond formation.
Nonribosomal peptide synthetase (NRPS): A multi-modular enzyme complex that assembles peptides independently of the ribosome by sequential activation and condensation of amino acid substrates.
Solid-phase peptide synthesis (SPPS): A stepwise method for constructing peptides on an insoluble resin support, enabling automated elongation and on-resin cyclisation.
References
- Avellanin A Has an Antiproliferative Effect on TP-Induced RWPE-1 Cells via the PI3K-Akt Signalling Pathway. Marine Drugs (2024).
- Micro-scale screening of genetically modified Fusarium fujikuroi strain extends the apicidin family. Natural Products and Bioprospecting (2024).
- Cyclic Tetrapeptides with Synergistic Antifungal Activity from the Fungus Aspergillus westerdijkiae Using LC-MS/MS-Based Molecular Networking. Antibiotics (2022).
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