Synthesis and characterization of a platinum-based antineoplastic agent by collision-induced dissociation tandem mass spectrometry
Poster Number
2B
Introduction/Abstract
Platinum-based antineoplastic agents are widely used in cancer chemotherapy. In this study, a novel Pt-HDACi conjugate by combining a key platinum intermediate K[PtCl3(2-picoline)] (TCPP) and a histone deacetylase inhibitor (HDACi) derivative (L01) was designed and synthesized. In comparison to Vorinostat (SAHA), structural derivations in L01 take places in the linker and cap domain. Mass spectrometry analysis was used to characterize the Pt-HDACi conjugate. The peaks at m/z (M+Na)+ and (M-•CH3+Na)+ ions were observed in the full-scan spectrum, suggested the successful synthesis of the Pt-HDACi complex. To obtain more detailed information about the binding of L01 to TCPP and the fragmentation pathway of the final complex, collision-induced dissociation tandem mass spectrometry (CID-MS/MS) using electron spray ionization mass spectrometer with a linear quadrupole ion trap analyzer was performed. The MS/MS spectrum of the precursor ion [M+Na]+ at m/z 620 revealed two prominent fragment ions under a collision energy of 20. A peak at m/z 584 corresponded to the loss of a chlorine atom from the molecule, while a peak at m/z 551 was due to the loss of hydroxylamine (NHOH). Another peak at m/z 483 was a fragment ion resulting from McLafferty rearrangement. The observed fragmentation patterns provided valuable information about the binding strength of each ligand and structural features of the Pt-HDACi conjugate.
Location
Library and Learning Center, 3601 Pacific Ave., Stockton, CA 95211
Format
Poster Presentation
Synthesis and characterization of a platinum-based antineoplastic agent by collision-induced dissociation tandem mass spectrometry
Library and Learning Center, 3601 Pacific Ave., Stockton, CA 95211
Platinum-based antineoplastic agents are widely used in cancer chemotherapy. In this study, a novel Pt-HDACi conjugate by combining a key platinum intermediate K[PtCl3(2-picoline)] (TCPP) and a histone deacetylase inhibitor (HDACi) derivative (L01) was designed and synthesized. In comparison to Vorinostat (SAHA), structural derivations in L01 take places in the linker and cap domain. Mass spectrometry analysis was used to characterize the Pt-HDACi conjugate. The peaks at m/z (M+Na)+ and (M-•CH3+Na)+ ions were observed in the full-scan spectrum, suggested the successful synthesis of the Pt-HDACi complex. To obtain more detailed information about the binding of L01 to TCPP and the fragmentation pathway of the final complex, collision-induced dissociation tandem mass spectrometry (CID-MS/MS) using electron spray ionization mass spectrometer with a linear quadrupole ion trap analyzer was performed. The MS/MS spectrum of the precursor ion [M+Na]+ at m/z 620 revealed two prominent fragment ions under a collision energy of 20. A peak at m/z 584 corresponded to the loss of a chlorine atom from the molecule, while a peak at m/z 551 was due to the loss of hydroxylamine (NHOH). Another peak at m/z 483 was a fragment ion resulting from McLafferty rearrangement. The observed fragmentation patterns provided valuable information about the binding strength of each ligand and structural features of the Pt-HDACi conjugate.
