We thank Evans (Chen) Ge, Mike (Dixin) Xue, and Simon (Junhua) Li at Chinese Peptide Company (CPC) for peptide synthesis support.
Abstract
Although stapled α-helical peptides can address challenging targets, their advancement is impeded by poor understandings for making them cell permeable while avoiding off-target toxicities. By synthesizing >350 molecules, we present workflows for identifying stapled peptides against Mdm2(X) with in vivo activity and no off-target effects. Key insights include a clear correlation between lipophilicity and permeability, removal of positive charge to avoid off-target toxicities, judicious anionic residue placement to enhance solubility/behavior, optimization of C-terminal length/helicity to enhance potency, and optimization of staple type/number to avoid polypharmacology. Workflow application gives peptides with >292x improved cell proliferation potencies and no off-target cell proliferation effects ( > 3800x on-target index). Application of these ‘design rules’ to a distinct Mdm2(X) peptide series improves ( > 150x) cellular potencies and removes off-target toxicities. The outlined workflow should facilitate therapeutic impacts, especially for those targets such as Mdm2(X) that have hydrophobic interfaces and are targetable with a helical motif.
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Chen, D., Mirski, M. A., Chen, S., Bryden, W. A., McLoughlin, M., Kiser, K. M., Caton, E. R., Haddaway, C. R., Cetta, M. S., & Pan, Y. PNAS nexus (2024), 3(9).
PEG36-Nle(O-Bzl)-Met(O)2-Oic-Abu-ACC was designed in house and synthesized by CPC Scientific Inc (San Jose, CA, Fig. S1). Amino-PEG36-acid (CAS: 196936-04-6) and 2-(7-amino-2-oxochromen-4-yl)acetamide (CAS:296236-23-2) were used for the synthesis. The synthesized sensor was resuspended in high-performance liquid chromatography (HPLC)-grade water with a concentration of 200 µM.
Chayanon Ngambenjawong, Henry Ko, Tahoura Samad, Novalia Pishesha, Hidde L. Ploegh, and Sangeeta N. Bhatia. ACS Nano 2025 19 (10), 9958-9970.
Therapeutic peptides and their Cy7-labeled analogs (Table S1 and Figure S14) were synthesized by CPC Scientific (CA, U.S.A.) via standard Fmoc-based SPPS.
Dakin, L.A., Xing, L., Hall, J. et al. Nat Commun 16, 4579 (2025).
The enzymatic reaction was started with the addition of 8 µM of substrate Atto655 - (Ser-Arg-Gly-Ala)3 (CPC Scientific Inc.) in assay buffer.
Olivia R. Buonarati, Nidia Quillinan, K. Ulrich Bayer. bioRxiv 2025.
tatCN19o. CPC Scientific; Coultrap et al. 2011. N/A (custom peptide).
J. Zeng, G.W.Z. Loi, E.N. Saipuljumri, M.A. Romero Durán, O. Silva-García, J.M. Perez-Aguilar, V.M. Baizabal-Aguirre, & C.H. Lo. Proc. Natl. Acad. Sci. U.S.A. 2024 121 (14).
FKC (FKCRRWQWRMKK-NH2), rhodamine-conjugated FKC (Rho-FKCRRWQWRMKK-NH2), and IDR (VQRWLIVWRIRK-NH2) peptides were synthesized using solid phase F-moc chemistry by CPC Scientific, Inc. with a purity greater than 95%.
Join us as we celebrate a proud milestone: the successful listing of Medtide Inc., parent company of CPC Scientific, on the main board of the Hong Kong Stock Exchange in June 2025. This moment marks a new chapter of growth, innovation, and global impact for our organization.
Gain insights from Joseph Denby's rapid-fire Q&A spotlight at NextGen Biomed, where he explores the landscape of peptide and oligo APIs, as well as the role of green chemistry in manufacturing.
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Highlights from CPC Scientific’s 2025 Annual Conference
GMP Peptide Manufacturing
We’re excited to share the key moments from CPC Scientific’s 2025 Annual Conference!
Hosted in San Jose, California, our annual gathering brought together colleagues from various teams and timezones for meaningful updates, focused […]
At NextGen Biomed 2025, Joseph Denby delivered a cutting-edge presentation highlighting the critical role green chemistry plays in the sustainable production of peptide APIs and peptide–oligo conjugates...