cyclic peptides in nature currently underexploited as chemical probes - Cyclic peptidessynthesis are derived from natural products Unveiling the Power of Cyclic Peptides in Nature: A Deep Dive into Their Structure, Bioactivity, and Applications

Cyclicpeptide blood test Cyclic peptides in nature represent a vast and fascinating class of molecules, renowned for their unique structures, potent bioactivity, and significant potential in various applications, particularly in drug development.作者：L Yang·2025·被引用次数：6—Here we report a platform for the rapid phenotypic selection of protein aggregation inhibitors from genetically encodedcyclic peptidelibraries in Escherichia ... These molecules, characterized by their circular or macrocyclic arrangement, are formed when the amino acid chain links back upon itself via amide bonds.Cyclic Peptides for Drug Development - Ji - 2024 This structural feature confers remarkable stability and often enhanced biological activity compared to their linear counterparts. The exploration of cyclic peptides has revealed them to be rich sources of natural bioactive agents, with a significant portion of current cyclic peptide drugs derived from natural products or their modifications.

The prevalence of cyclic peptides in nature is extraordinary, with these compounds widely found in nature across diverse sources such as bacteria, fungi, plants, and marine speciesa knowledge base of natural and synthetic cyclic peptides. This ubiquity underscores their evolutionary significance and their role in various ecological processes. The total synthesis of naturally occurring cyclic peptides has been a major focus in recent years, enabling researchers to study their intricate structures and bioactivities in detail. For instance, the total synthesis of naturally occurring cyclic peptides such as darobactin, a potent antibiotic, highlights the complex chemical architectures that nature can produce. Furthermore, the total synthesis and biological evaluation of natural cyclic peptides are crucial for understanding their therapeutic potential.

The inherent stability of cyclic peptides makes them particularly attractive for drug developmentin small cyclic peptides. Unlike linear peptides, which are susceptible to enzymatic degradation in the body, the cyclic structure of these molecules offers increased resistance to proteases, leading to longer circulation times and improved bioavailability. This characteristic allows cyclic peptides to bind challenging disease targets with high affinity and specificity, opening up avenues for treating conditions that are difficult to address with conventional small molecules.作者：K Bajaj·2019·被引用次数：16—Natural cyclic peptides and peptidomimetics arerich sources of natural bioactive agents. Their exceptionally high stability and potent bioactivity compared to ... The ability of cyclic peptides to target challenging disease targets is a key driver in their increasing importance in drug discovery.

A significant area of research involves cyclic peptides found in plants, such as cyclic plant peptides like cyclotides. These peptides, typically around 30 amino acids long, are characterized by a conserved cysteine knot motif formed by three disulfide bonds, contributing to their exceptional stability and diverse biological activities, including antimicrobial and anti-cancer properties.作者：BL Santini·2024·被引用次数：4—Cyclic peptides have emerged as versatile scaffolds in drug discoverydue to their stability and specificity. Here, we present the cPEPmatch ... The study of naturally occurring cyclic peptides also extends to naturally occurring and rationally designed cyclic tetrapeptides, which have demonstrated a range of biological effects.

The versatility of cyclic peptides is further emphasized by their role as chemical probes. Their ability to be programmed to fold or self-assemble into diverse structures makes them valuable tools for investigating biological processes. Moreover, cyclic peptides are fascinating molecules abundantly found in nature and have been successfully exploited as molecular formats for drug development and other applications.Recent highlights of the total synthesis of cyclic peptide ... The development of cyclic peptides that can be administered orally is an ongoing area of research, aiming to overcome limitations related to digestion and absorptionTarget-based de novo design of cyclic peptide binders.

The discovery and biosynthesis of cyclic plant peptides and other natural cyclic peptides are continually expanding our understanding of these molecules.作者：T Doi·2025·被引用次数：1—This review described thetotal synthesis of naturally occurring cyclic peptideswith unique structures covering 2020 to 2022, i.e., darobactin ... Researchers are actively developing computational approaches for the de novo design of cyclic peptides that can bind to specific protein surfaces with high affinity, a critical step in creating novel therapeutic agents. The field of cyclic peptide design leverages knowledge of natural structures and functionalities to create synthetic analogs with improved properties.

In clinics, several cyclic peptides found in nature are already in use. Notable examples include gramicidin and tyrocidine, known for their bactericidal activity, and cyclosporin A, an immunosuppressant widely used in organ transplantation. These successful applications demonstrate the therapeutic promise of cyclic peptides. The development of methods for the rapid discovery of cyclic peptide protein aggregation inhibitors from genetically encoded libraries further showcases their potential in tackling complex diseases.

The exploration of cyclic peptides in nature is an ongoing journey, revealing cyclic peptides as an exciting class of compounds that are currently underexploited as chemical probes. Their stability and specificity make cyclic peptides versatile scaffolds in drug discovery, and ongoing research into their synthesis, design, and biological evaluation promises to unlock even greater therapeutic potential. As our understanding deepens, cyclic peptides will undoubtedly continue to play a pivotal role in advancing medicine and biotechnology.