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Carbohydrate‐linked cisplatin analogue: reactivity studies with RNA and DNA
Author(s) -
Gamage Supuni Duneeshya Thalalla,
Muthunayake Nisansala,
Sonousi Amr,
Crich David,
Chow Christine
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.608.8
Subject(s) - cisplatin , chemistry , nucleic acid , dna , rna , reactivity (psychology) , mass spectrometry , biochemistry , combinatorial chemistry , chromatography , medicine , chemotherapy , gene , alternative medicine , pathology , surgery
With the discovery of cisplatin in the 1960s, it has been widely studied as a precursor for anticancer drug development. Despite its effectiveness against certain cancers, clinical usage of cisplatin is restricted by a number of side effects and resistance. In the past decade, scientists have been exploring biologically important ligands such as sugar derivatives in the hope of overcoming such challenges. Attachment of a sugar moiety could facilitate lower accumulation of platinum drugs in the body as well as enhance cellular uptake. In this study, a carbohydrate‐linked cisplatin analogue, cis ‐dichloro[(2‐ β ‐D‐glucopyranosidyl)propane‐1,3‐diamine]platinum ( 1 ) has been studied. The aim is to evaluate the binding targets and mechanism of action compared to cisplatin. Compound 1 was synthesized and a reactivity study was carried out with deoxy‐/ribonucleosides and nucleic acids using high performance liquid chromatography (HPLC), liquid chromatography mass spectrometry (LC‐MS), and matrix‐assisted laser‐desorption ionization mass spectrometry (MALDI‐MS). A study was done to analyze the effects of compound 1 on DNA duplex structure by measuring the bending angles. Further probing studies on ribosomal RNA showed compound 1 localization on rRNA. Overall, this work allows us to compare ligand binding and subsequent effects on nucleic acids through a series of chemical and biochemical techniques. Support or Funding Information Wayne State University‐Faculty Schaap Fellowship