Abstract
We report novel polymyxin analogues with improved antibacterial in vitro potency against polymyxin resistant recent clinical isolates of Acinetobacter baumannii and Pseudomonas aeruginosa . In addition, a human renal cell in vitro assay (hRPTEC) was used to inform structure-toxicity relationships and further differentiate analogues. Replacement of the Dab-3 residue with a Dap-3 in combination with a relatively polar 6-oxo-1-phenyl-1,6-dihydropyridine-3-carbonyl side chain as a fatty acyl replacement yielded analogue 5x, which demonstrated an improved in vitro antimicrobial and renal cytotoxicity profiles relative to polymyxin B (PMB). However, in vivo PK/PD comparison of 5x and PMB in a murine neutropenic thigh model against P. aeruginosa strains with matched MICs showed that 5x was inferior to PMB in vivo, suggesting a lack of improved therapeutic index in spite of apparent in vitro advantages.
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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...