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Peptide Drug Conjugates (PDC) Development for Pancreatic Cancer

Peptide Drug Conjugates (PDC) Development for Pancreatic Cancer

Peptide drug conjugates (PDCs) utilize the specificity of peptides to release cytotoxic loads directly to cancer cells. Alfa Cytology aims to develop targeted therapies that inhibit pancreatic tumor growth, induce apoptosis, and attenuate tumor heterogeneity using PDC technology.

Introduction to Peptide Drug Conjugates

Peptide drug conjugates (PDCs) are a class of therapeutic agents that combine the targeting specificity of peptides with the high potency of small molecule drugs. These conjugates consist of a peptide moiety attached to a small molecule drug through a linker molecule, allowing for selective delivery of the drug to specific cells or tissues. The small molecule drug in a PDC is typically a potent therapeutic agent with low bioavailability or poor target selectivity. By conjugating the drug to a peptide, its pharmacokinetic properties can be improved, leading to better therapeutic outcomes.

Fig. 1 Mechanisms of anti-cancer peptides.Fig. 1 A schematic of a peptide–drug conjugate structure. (Fu C, 2023)

Linkers Used in Peptide Drug Conjugates

The linker molecule in a PDC plays a crucial role in controlling the release of the drug at the target site. It must be stable in circulation to prevent premature release of the drug, but also cleavable under specific conditions (such as low pH or enzymatic activity) to allow for controlled drug release once the PDC reaches its target. Various types of linkers can be used depending on the desired release profile of the drug.

Linker Type Name
Non-cleavage Carbon chain, Amido bond, Ether bond
pH sensitive Hydrazone bond, Vinyl ether bond, Acetal/Ketal bond
Enzyme sensitive Disulfide bond
Redox sensitive Gly-Phe-Leu-Gly, Val-Cit (Cit=Citrulline), Phe-Lys

Peptide Drug Conjugates Development for Pancreatic Cancer

Pancreatic cancer is one of the most lethal types of cancer with limited treatment options. However, several approved PDCs are now available for the treatment of pancreatic cancer, offering renewed hope for patients battling this aggressive disease.

Peptide Drug Conjugates Introduction
Pegilodecakin (AM0010) Pegilodecakin is a PEGylated form of interleukin-10 (IL-10) that targets the tumor microenvironment in pancreatic cancer.
Pasireotide-tyrosine-3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (SSTR)-conjugate This PDC combines pasireotide, a somatostatin analog, with a targeting peptide specifically directed against SSTR, a receptor overexpressed in pancreatic neuroendocrine tumors.
Gemcitabine-ABD-fibrin/hyaluronic acid-conjugate Through conjugation with an antifibronectin single-chain antibody fragment, this PDC specifically targets tumor-associated fibronectin overexpression, resulting in enhanced delivery of gemcitabine to the tumor site.

Our Services

Alfa Cytology's service encompasses peptide design, linker optimization, conjugation chemistry, and preclinical evaluation, ensuring the seamless translation of innovative PDCs from concept to application. Our research focuses on optimizing peptide-drug linkers, enhancing conjugate stability, and exploring novel peptide targets for pancreatic cancer treatment.

Peptide Sequence Design Service

  • Sequence Selection: Identify specific biomarkers or receptors overexpressed on pancreatic cancer cells.
  • Bioinformatics Analysis: Utilize computational tools to design peptides with high binding affinity and specificity.
  • Structural Optimization: Incorporate structural modifications to enhance stability and binding interactions.
  • Experimental Validation: Validate peptide designs through in vitro assays to assess binding affinity and selectivity.
  • Iterative Optimization: Iteratively refine peptide sequences based on experimental feedback for improved efficacy.

Workflow of Candidate Peptide Drug Conjugates Development

Payload Selection

Choose cytotoxic drugs based on efficacy and mechanism of action against pancreatic cancer.

Linker Design

Optimize linker chemistry for stable conjugation between peptide and cytotoxic payload.

Conjugation Chemistry

Employ bioconjugation techniques such as click chemistry or amide bond formation.

Purification

Purify PDCs to remove unconjugated peptides and ensure batch-to-batch consistency.

Characterization

Characterize PDCs for drug-to-peptide ratio, stability, and purity.

Preclinical Evaluation Service for Peptide Drug Conjugates

Cellular Assays

Assess cytotoxicity and efficacy of PDCs using pancreatic cancer cell lines.

Animal Models

Evaluate PDCs in animal models to simulate human disease conditions.

Pharmacokinetics & Pharmacodynamics

Study drug distribution, metabolism, and efficacy profiles in vivo.

Toxicity Studies

Conduct safety assessments to evaluate potential adverse effects.

Why Choose Us?

Tailored Solutions

Advanced Technology

Professional Expertise

Collaborative Approach

Alfa Cytology is committed to advancing PDC development, offering cutting-edge solutions that harness the power of peptides to combat pancreatic cancer. Contact us to explore collaborative opportunities and accelerate the development of innovative PDC therapies for pancreatic cancer patients.

Reference

  1. Fu C, et al. Peptide–drug conjugates (PDCs): a novel trend of research and development on targeted therapy, hype or hope? Acta Pharmaceutica Sinica B. 2023, 13(2): 498-516.
All of our services are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.