The synthesis of the linear RP-182 analog, bicyclo[6.1.0]non-4-yn-9-ylmethyloxycarbonyl-PEG2-Lys-Phe-Arg-Lys-Ala-Phe-Lys-Arg-Phe-Phe-Lys(azido-PEG)-NH2, was achieved using standard solid-phase peptide synthesis (SPPS) protocols. After cleaving the linear peptide from the resin, macrocyclization was performed in the liquid phase through a strain-promoted click reaction. BCN introduces extra ring strain due to its fused cyclopropane structure. The combined effect of ring strain, the selection of BCN, and copper catalysis significantly increases the macrocyclization efficiency of longer peptides like RP-182.
Singh, S.S., Calvo, R., Kumari, A., Sable, R.V., Fang, Y., Tao, D., Hu, X., Castle, S.G., Nahar, S., Li, D. and Major, E. Molecular Cancer Therapeutics (2024).
- CPC Scientific Inc., 160E Tasman Dr., Suite 200, San Jose, CA 95134
[..] assembling the peptide on the Rink Amide resin and attaching the PEG azide moiety to the N-terminal Lys, the Dde group was removed as previously shown and coupled to the Fmoc-PEG2-acid. Removal of the Fmoc followed by simultaneously click/coupling to bicyclo[6.1.0]non-4-yn-9-ylmethyl (2,5-dioxopyrrolidin-1-yl) carbonate gave 1c which was deprotected and cleaved from the resin to give 1c.
Liu, J., Heddleston, J., Perkins, D.R., Chen, J.J.H., Ghanbarpour, A., Smith, B.W., Miles, R., Aihara, E. and Afshar, S. Scientific Reports 14, no. 1 (2024): 13437.
- Protein Engineering, Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA, 92121, USA
- Biotechnology Research, Lilly Corporate Center, Eli Lilly and Company, Indianapolis, IN, 46221, USA
- Genetic Medicine, Lilly Corporate Center, Eli Lilly and Company, Indianapolis, IN, 46221, USA
Synthetic peptides were ordered from CPC scientific with > 95% purity. NNJA peptides in the formats of monomer or dendrimer were conjugated by click chemistry to siRNA targeting hypoxanthine–guanine phosphoribosyltransferase (HPRT) gene [..]
Hao, Liangliang, Natalie Boehnke, Susanna K. Elledge, Nour-Saïda Harzallah, Renee T. Zhao, Eva Cai, Yu-Xiong Feng et al. Proceedings of the National Academy of Sciences 121, no. 11 (2024): e2307802121.
The azido-modified biosensor peptide (sequence B(biotin)-eGvndneeGffsarK-(FAM)dGGPLGVRGKK-(N3)) was synthesized by CPC Scientific with >90% purity.
Design-rules for stapled peptides with in vivo activity and their application to Mdm2/X antagonists.
Chandramohan, A., Josien, H., Yuen, T.Y., Duggal, R., Spiegelberg, D., Yan, L., Juang, Y.C.A., Ge, L., Aronica, P.G., Kaan, H.Y.K. and Lim, Y.H. Nature Communications 15, no. 1 (2024): 489.
- Merck & Co., Inc., Kenilworth, NJ 07033, USA.
- Merck & Co., Inc., Boston, MA 02115, USA
- Merck & Co., Inc., West Point, PA 19486, USA
- Genentech, South San Francisco, CA 94080, USA
We thank Evans (Chen) Ge, Mike (Dixin) Xue, and Simon (Junhua) Li at Chinese Peptide Company (CPC) for peptide synthesis support.
Paul S. Marinec, Kyle E. Landgraf, Maruti Uppalapati, Gang Chen, Daniel Xie,‡ Qiyang Jiang, Yanlong Zhao, Annalise Petriello, Kurt Deshayes, Stephen B. H. Kent, Dana Ault-Riche*, and Sachdev S. Sidhu* ACS Chem. Biol. 2021, 16, 3, 548–556.
- Chinese Peptide Company, Hangzhou Economic and Technical Development Zone, China, 310018.
"The D-VEGF-A polypeptide chain (COOH acid, residues 8-109 (1)) was chemically synthesized using solid phase peptide synthesis (SPPS) and native chemical ligation, and folded to form the protein covalent homodimer, using methods adapted from our previous work [..]"
Hao, Liangliang, Renee T. Zhao, Chayanon Ngambenjawong, Heather E. Fleming, and Sangeeta Bhatia. bioRxiv (2020).
All peptides were chemically synthesized by CPC Scientific, Inc. [..] K(N3)-ANP-GPVPLSLVMGGC [..] 5FAM-GGf-Pip-KSGGGK(CPQ2)-PEG2-GC
Vickers, Timothy A., Meghdad Rahdar, Thazha P. Prakash, and Stanley T. Crooke. Nucleic Acids Research (2019).
A solution of 1.5 umol SmBiT peptide (Val-Thr-Gly-Tyr-Arg-Leu-Phe-Glu-Glu-Ile-Leu-Gly-Gly-Ser-Gly-Gly-Lys(N3)-NH2) containing an azide group at the C-terminus (CPC Scientific, 1245 Reamwood Ave, Sunnyvale, CA, USA) in DMSO (0.5 ml) was added and the reaction mixture was stirred at room temperature for 5 h.
Puthenveetil, Sujiet, et al. PloS One 12.5 (2017): e0178452.
- Worldwide Medicinal Chemistry, Pfizer Global R&D, Groton, Connecticut, United States of America.
- Pfizer Oncology Research, Pearl River, NY, United States of America.
"Peptide-payload conjugate (7) was prepared by reacting 2mM aizoacetyl-Ser-Lys-Gly-Ser-Lys (CPC scientific, inc. Sunnywale, CA) with 8 mM NHS-ester payload [19] in 50% Dimethyl sulfoxide (DMSO), 50 mM borate buffer pH 8.5 for 2 h at 37°C."
Novel theranostic nanoporphyrins for photodynamic diagnosis and trimodal therapy for bladder cancer.
Lin, Tzu-Yin, et al. Biomaterials 104 (2016): 339-351.
"Our previously reported PLZ4-PEG 5k -CA 8 telodendrimer was synthesized by the conjugation of alkyne-derivatized bladder cancer targeting ligand PLZ4 (CPC Scientific, Sunnyvale, CA)"
