Preparation of Ligand-Targeted DrugConjugates for Cancer Therapy andTheir Evaluation In Vitro

摘要

Present treatment strategies focus on minimizing unwanted toxicity to healthycells during chemotherapeutic treatment. This is achieved by developing strategiesto selectively deliver drugs to malignant cells over-expressing specific proteinbiomarkers. The drugs are attached via a self-immolative linker to a smallmolecule homing ligand having affinity for protein biomarkers over-expressedduring disease states. Several such targeting-ligand drug conjugates have nowreached preclinical and clinical trials, and this article aims to show a generalmethodology to prepare the same. Using solid-phase peptide synthesis (SPPS)methodology, the targeting ligand is covalently linked to a peptide spacer havingappropriate hydrophobic and hydrophilic amino acids. The targeting ligand–attached peptide spacer is next conjugated with the required drug moleculethrough a cleavable disulfide bond in a solution-phase reaction. This protocolfurther elucidates the step-by-step procedures to be followed for complete evaluationof newly synthesized ligand-targeted drug conjugates in vitro.