"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)"
Abstract
The overall prognosis of bladder cancer has not been improved over the last 30 years and therefore, there is a great medical need to develop novel diagnosis and therapy approaches for bladder cancer. We developed a multifunctional nanoporphyrin platform that was coated with a bladder cancer-specific ligand named PLZ4. PLZ4-nanoporphyrin (PNP) integrates photodynamic diagnosis, image-guided photodynamic therapy, photothermal therapy and targeted chemotherapy in a single procedure. PNPs are spherical, relatively small (around 23 nm), and have the ability to preferably emit fluorescence/heat/reactive oxygen species upon illumination with near infrared light. Doxorubicin (DOX) loaded PNPs possess slower drug release and dramatically longer systemic circulation time compared to free DOX. The fluorescence signal of PNPs efficiently and selectively increased in bladder cancer cells but not normal urothelial cells in vitro and in an orthotopic patient derived bladder cancer xenograft (PDX) models, indicating their great potential for photodynamic diagnosis. Photodynamic therapy with PNPs was significantly more potent than 5-aminolevulinic acid, and eliminated orthotopic PDX bladder cancers after intravesical treatment. Image-guided photodynamic and photothermal therapies synergized with targeted chemotherapy of DOX and significantly prolonged overall survival of mice carrying PDXs. In conclusion, this uniquely engineered targeting PNP selectively targeted tumor cells for photodynamic diagnosis, and served as effective triple-modality (photodynamic/photothermal/chemo) therapeutic agents against bladder cancers. This platform can be easily adapted to individualized medicine in a clinical setting and has tremendous potential to improve the management of bladder cancer in the clinic.
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CPC Scientific at DCAT 2025!
GMP Peptide Manufacturing
What an amazing time we had at DCAT 2025! It was fantastic to meet with colleagues, clients, and friends, and showcase CPC Scientific’s cutting-edge capabilities in synthetic API development and commercial production.
A heartfelt […]
We are excited to share that CPC Scientific Inc. has officially received the Good Manufacturing Practice (GMP) Certificate in accordance with the ISO 22716:2007(E) Cosmetic Guidelines.
This certification highlights our unwavering commitment to delivering the highest quality peptide ingredients for cosmetic use, guaranteeing:
- Superior Quality Control – Striving for excellence in safety, consistency, and purity.
[…]
In Part 1 of our Minimal Protection Group Strategies for SPPS, we discussed methods for eliminating sidechain protection on hydroxy-bearing amino acids such as serine, threonine, tyrosine, and hydroxyproline. By omitting t-butyl protection, we enhanced atom economy and avoided the use of hazardous solvents typically required to remove these protection groups. In Part 2, we present a new case study, expanding our approach to include the unprotected side chains of histidine, tryptophan, and arginine. We demonstrate the synthesis of a Goserelin peptide API impurity, showcasing how a convergent peptide fragment strategy can be used to eliminate the need for TFA and diethyl ether, eliminate side chain protection of Arginine, Histidine, and Tryptophan.
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.
Nakagawa, Mayumi, Teresa Evans, Milan Bimali, Hannah Coleman, Jasmine Crane, Nadia Darwish, Jennifer L. Faulkner et al. MedRxiv (2025): 2025-01.
The vaccine consisted of four current good manufacturing production-grade synthetic peptides covering the HPV 16 E6 protein [amino acid (aa)1-45, 46-80, 81-115, and 116-158] (CPC Scientific, San Jose, CA [..]
Stapled peptides have emerged as a powerful tool in drug discovery and therapeutic development due to their ability to overcome the limitations associated with traditional peptide drugs, such as poor stability and low cell permeability. By introducing staples into the peptide backbone, researchers can stabilize peptide conformations and enhance their interactions with target proteins, resulting in improved efficacy and specificity. This approach not only addresses the challenges of peptide drug design but also opens new avenues for targeting challenging biomolecular interactions that are difficult to modulate with small molecules or antibodies. The development of stapled peptides has led to significant advancements in targeting protein-protein interactions, addressing previously intractable diseases, and enhancing the precision of therapeutic interventions.
Peptide receptor radionuclide therapy (PRRT) is a targeted therapeutic approach that utilizes peptides to deliver cytotoxic radiation to specific receptors overexpressed on cancer cells. Peptides offer several advantages as therapeutic vectors in PRRT due to their small size, favorable pharmacokinetics, high binding affinity, low immunogenicity and toxicity, and minimal off-target effects. Tumor-targeting peptides conjugated to radionuclide chelates represent a promising class of cancer therapeutics.
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.
Most proteinogenic peptides, except for certain hydrophobic sequences, can be synthesized in a linear fashion using solid-phase peptide synthesis (SPPS) methods. However, longer sequences, particularly those exceeding 70 amino acids, often require alternative techniques due to challenges like steric hindrance. Other issues, such as poor solvation of the protected peptide during synthesis and the formation of intermolecular hydrogen bonds (e.g., β-sheets) between fragments, can also result in inefficient coupling and deprotection.