title: Raman spectroscopic evaluation of DNA adducts of a platinum containing anticancer drug.
abstract: Mechanistic understanding of the interaction of drugs with their target molecules is important for better understanding of their mode of action and to improve their efficacy. Carboplatin is a platinum containing anticancer drug, used to treat different type of tumors. In the present work, we applied Raman spectroscopy to study the interaction of carboplatin with DNA at molecular level using different carboplatin-DNA molar ratios. These Raman spectroscopic results provide comprehensive understanding on the carboplatin-DNA interactions and indicate that DNA cross-linked adducts formed by carboplatin are similar to cisplatin adducts. The results indicate that guanine N7 and adenine N7 are the putative sites for carboplatin interaction. It is observed that carboplatin has some affinity toward cytosine in DNA. Phosphate sugar backbone of DNA showed conformation perturbation in DNA which were easily sensible at higher concentrations of carboplatin. Most importantly, carboplatin interaction induces intermediate A- and B-DNA conformations at the cross-linking sites.
authors.affiliation: Quantum Optics and Photon Physics, CSIR-National Physical Laboratory, Dr. K.S. Krishnan Road, New Delhi 110012, India.
authors.forename: Deepak K
authors.initials: DK
authors.lastname: Jangir
authors.affiliation: Quantum Optics and Photon Physics, CSIR-National Physical Laboratory, Dr. K.S. Krishnan Road, New Delhi 110012, India. Electronic address: Ranjana@nplindia.org.
authors.forename: Ranjana
authors.initials: R
authors.lastname: Mehrotra
mesh_terms: D000225:Adenine / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D016190:Carboplatin / Q000737:chemistry*; D002417:Cattle; D002945:Cisplatin / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry; D004247:DNA / Q000737:chemistry; D018736:DNA Adducts / Q000737:chemistry*; D006147:Guanine / Q000737:chemistry; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D009690:Nucleic Acid Conformation; D010984:Platinum / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman; D013950:Thymus Gland / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D018736:DNA Adducts; D010984:Platinum; D006147:Guanine; D004247:DNA; D016190:Carboplatin; D000225:Adenine; D002945:Cisplatin
keywords: Calf-thymus DNA; Carboplatin; Carboplatin–DNA interaction; FT-Raman spectroscopy