Abstract

Cancer is a major health issue adsorbing the attention of a biomedical research. To fight this disease, new drugs are developed, specifically tailored to target biological pathways or peculiar components of the tumour cells. Particularly interesting is the use of intercalating agents as drugs capable to bind DNA and inhibit enzymes involved in DNA metabolism. Anthracyclines are the most commonly used anticancer drugs. In particular, daunomycin is used to cancer treatment by exploiting its ability to intercalate DNA and inhibit the activity of DNA topoisomerases implicated in the replication processes. Unfortunately, clinical application of anthracyclines is limited by their side effects. The conjugation with specific carriers could affect the selectivity and reduce side effect by improving stability and/or cellular uptake properties. We here report the biochemical characterisation of a daunomycin oligopeptide conjugate containing six residues of arginine, by the analysis of its fluorescence properties, DNA interaction and topoisomerases inhibitory effects.

摘要

癌症是吸引生物医学研究关注的主要健康问题。为了对抗这种疾病，开发了专门针对肿瘤细胞的生物途径或特殊成分的新药。特别令人感兴趣的是使用插层剂作为能够结合DNA并抑制DNA代谢相关酶的药物。蒽环类药物是最常用的抗癌药物。特别地，道诺霉素通过利用其嵌入DNA并抑制复制过程中涉及的DNA拓扑异构酶活性的能力而用于癌症治疗。不幸的是，蒽环类药物的临床应用受到其副作用的限制。与特定载体的缀合可以通过提高稳定性和/或细胞摄取特性来影响选择性并减少副作用。