Synthesis and Investigation of Peptide-Drug Conjugates Comprising Camptothecin and a Human Protein-Derived Cell-Penetrating Peptide.

ABSTRACT: Drug targeting strategies, such as peptide-drug conjugates (PDCs), have arisen to combat the issue of off-target toxicity that is commonly associated with chemotherapeutic small molecule drugs. Here we investigated the ability of PDCs comprising a human protein-derived cell-penetrating peptide-platelet factor 4-derived internalization peptide (PDIP)-as a targeting strategy to improve the selectivity of camptothecin (CPT), a topoisomerase I inhibitor that suffers from off-target toxicity. The intranuclear target of CPT allowed exploration of PDC design features required for optimal potency. A suite of PDCs with various structural characteristics, including alternative conjugation strategies (such as azide-alkyne cycloaddition and disulfide conjugation) and linker types (non-cleavable or cle

SUBMITTER: Palombi IR 

PROVIDER: S-EPMC11747586 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature