title: Characterization of antisense oligonucleotide-peptide conjugates with negative ionization electrospray mass spectrometry and liquid chromatography-mass spectrometry.
abstract: Covalent post-synthesis or solid-phase conjugation of peptides to oligonucleotides has been reported as a possible method of delivering antisense oligonucleotides into cells. While synthesis strategies for preparing these conjugates have been widely addressed, few detailed reports on their structural characterization have been published. This paper discusses the negative ion electrospray ionization mass spectrometric (ESI-MS) and liquid chromatography-mass spectrometric (LC-MS) analysis of various peptide-oligonucleotide conjugates ranging from small T(6)-nucleopeptides to large peptide-oligonucleotide phosphorothioate conjugates and ribozyme-peptide hybrids (3-13 kDa). Molecular weight determination with mass errors of 0.1-3.1 amu were conducted, employing on-line IP-RP-HPLC and high m/z range mode to facilitate the analysis of large compounds and difficult modifications.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland.
authors.forename: Unni
authors.initials: U
authors.lastname: Tengvall
authors.forename: Seppo
authors.initials: S
authors.lastname: Auriola
authors.forename: Maxim
authors.initials: M
authors.lastname: Antopolsky
authors.forename: Alex
authors.initials: A
authors.lastname: Azhayev
authors.forename: Leo
authors.initials: L
authors.lastname: Biegelman
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D016376:Oligonucleotides, Antisense / Q000032:analysis* / Q000737:chemistry; D010455:Peptides / Q000032:analysis* / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D016376:Oligonucleotides, Antisense; D010455:Peptides