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Unlocking the Potential of Cyclic Peptide Therapeutics: Viva Biotech's Discovery Insights


News provided by

Viva Biotech

02 Sep, 2025, 09:30 GMT

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SHANGHAI, Sept. 2, 2025 /PRNewswire/ -- Peptides have recently emerged at the forefront of therapeutic innovation, with cyclic peptides gaining particular attention for their ability to bridge the gap between small molecules and large biologics. Positioned between the two, cyclic peptides combine the oral potential of small molecules with the structural advantages of biologics—making them ideally suited to address traditionally "undruggable" protein–protein interactions and complex receptors, while opening new avenues for oral drug discovery. With global investment in peptide pipelines steadily increasing, cyclic peptides are becoming a therapeutic frontier of rising importance.

As the latest session in the ongoing Viva BioInsights webinar series, Medicinal Chemistry for Cyclic Peptide Drug Discovery, featuring Dr. Kejia Ding, Executive Director of Chemistry, and moderated by Mr. Simon Bury, Vice President of Business Development. The webinar attracted strong global interest, offering in-depth perspectives on how medicinal chemistry shapes cyclic peptide drug discovery—highlighting both the opportunities and challenges of this modality, illustrated through case studies and Viva's integrated capabilities.

Cyclic Peptides: Bridging Small Molecules and Biologics

Cyclic peptides are increasingly recognized as an attractive drug modality to tackle traditionally "undruggable" targets. They combine the oral potential of small molecules with the structural advantages of biologics, enabling new approaches for protein–protein interactions and complex receptors. At the same time, they present key challenges: oral bioavailability is not easily achieved, and stability and permeability must be carefully optimized with a clear medicinal chemistry strategy.

Viva Biotech supports cyclic peptide discovery with in-house phage display and a DEL library of cyclic peptides, alongside AI-based methods for structure prediction, sequence redesign, and de novo design. Structure determination and prediction leverage NMR, X-ray crystallography, molecular-dynamics simulations, and deep-learning models. On the chemistry side, the team applies various modifications to optimize stability, permeability, and in-vivo exposure, such as N-methylation scans, non-natural amino acids, backbone and side-chain modifications, and bi-/tri-cyclic architectures.

Case Studies: From Nature's Insights to Engineered Innovation

Cyclosporine A

As a natural-product immunosuppressant, cyclosporine A illustrates how a highly hydrophobic cyclic peptide can still achieve oral exposure (~30%). Structural studies across solvents and co-crystals reveal environment-dependent conformational switching (open form vs. β-sheet–like closed form; cis/trans amide), offering a mechanistic explanation for its membrane permeability and oral bioavailability. Importantly, increases in in-vitro binding do not necessarily translate into cell activity, and small structural changes can cause large differences in permeability and pharmacokinetics.

MK-0616

In contrast, MK-0616 exemplifies a Medicinal Chemistry approach to develop an oral tri-cyclic peptide drug. After obtaining the linear peptide hit from mRNA display, the development process includes cyclization, early peptide SAR scans (alanine, D-amino acid, N-methylation), side-chain/backbone tuning, and bi-/tri-cyclic designs guided by co-crystal structures, while largely maintaining the macrocycle's binding-competent conformation. Published studies reported that, with Labrasol-enabled oral dosing and statin co-treatment, MK-0616 achieved long half-lives (35–130 h; F% <5%) along with >80% PCSK9 reduction and ~65% LDL-C lowering.

Together, these cases highlight key features of natural orally bioavailable cyclic peptide and how structure-guided design and medicinal chemistry can develop an orally bioavailable cyclic peptide drug.

From Integrated Capabilities to Future Innovation

Viva Biotech has established a one-stop platform for peptide drug discovery and development, covering hit discovery to preclinical candidates. To date, Viva Biotech has delivered over 82,000 protein structures that inform structure-based design, and synthesized more than 3,000 peptides—over 80% of which are cyclic. This platform integrates DEL screening (including cyclic peptide libraries), phage display, AI-enabled peptide design, automated chemical synthesis, bioassays, and DMPK studies, complemented by backbone modifications, non-natural amino acids, stapling, PEG/lipid conjugation, and advanced analytical and purification technologies.

As Dr. Ding emphasized, it is the integration of methods and tools—from libraries and computation to synthesis and analysis—that makes cyclic peptide discovery practical at scale. Looking ahead, Viva Biotech will continue to work with global partners to harness cyclic peptides as a therapeutic frontier, accelerating the translation of structural insights into real-world therapeutics.

Webinar replay: https://youtu.be/bCx6ezGGH-M

For more information about Viva Biotech's integrated drug discovery services, please visit www.vivabiotech.com.

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