As a leading CRO, BOC Sciences has been supporting customers at the forefront of drug conjugation. Peptide-drug conjugate (PDC) is an emerging promising class of targeted therapeutics. We offer peptide drug conjugation services to accelerate your peptide drug development. Our scientific team has expertise in peptide conjugation chemistry and is capable of meeting your unique project needs.
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The principle of peptide-drug conjugate (PDC) is to conjugate cell-targeting peptides with drug molecules to enhance drug targeting and to concentrate the drug in the target tissue, thus reducing its relative concentration in other tissues, increasing effectiveness and reducing adverse effects. The peptides used in PDCs include cell-targeting peptides (CTPs) and cell-penetrating peptides (CPPs). Various linkers have been used in PDCs development to prevent unspecific release of the drug. Payloads available in the PDCs include cytotoxic drugs and radionucleotides. PDC integrates the advantages of peptides with low molecular weight and biodegradability, while not causing immunogenic reactions.
Fig 1. Peptide-drug conjugate (Cooper, 2021)
Peptides selected for PDCs should have the ability to specifically target protein receptors overexpressed in tumor tissue and have strong binding affinity for the target site within nanomolar amounts. Most of the peptides reported so far are linear peptides showing good binding. In addition, the binding affinity of peptides can be increased by stabilizing secondary structures such as α-helix and β-sheet.
|RGD (arginine-glycine-aspartic acid)||Integrins (α5β1, α8β1 and αIIbβ3)|
|GnRH (gonadotropin-releasing hormone)||GnRH-R (receptor version of the hormone)|
|SST (somatostatin)||SSTR1-5 (somatostatin receptor)|
|EGF (epidermal growth factor)||EGFR: HER1, HER2, HER3, HER4|
|Angiopep-2||LRP-1 (low-density lipoprotein receptor-related protein-1)|
Table 1. Examples of peptides used in PDCs
Although a peptide can provide many properties to PDC, including enhanced tumor penetration, reduced immunogenicity, and cheaper synthesis, the relatively small size of peptide allows for fast renal clearance of PDC. This problem can be addressed by various methods, such as chemical modification (e.g. peptide dendrimers) and physical techniques (e.g. combination of the PDC with nanoparticles).
PDC drugs are mainly used in anti-cancer therapy. Peptide part is used for the targeted delivery of anticancer drug molecules and to reduce systemic toxicity. In some cases, PDC employs cell-penetrating peptides, which can facilitate the proper translocation of anticancer drugs across cell membranes to their desired sites.
In addition to improving pharmacological properties, PDCs can also be used for cancer diagnostics. In this case, the tumor-selective peptides are conjugated to fluorescent dyes, the peptides readily bind to specific receptors on tumor cells, and the fluorescent dyes make imaging of cancer tissue feasible.