title: [Intracomplex alkylation of octanucleotide pd(TGTTTGGC) by a 5'-(4-N-methyl-N-(2-chloroethyl)-amino)benzylphosphamide derivative of heptanucleotide pd(CCAAACA). Preparation of a covalent adduct and study of its spatial structure in an aqueous solution by two-dimensional (1)H-NMR spectroscopy].
abstract: Covalent adduct--the product of intracomplex alkylation at N-3-position of dC-8-nucleoside residue of target octanucleotide pd[TGTTTGGC] was completely synthesized by means of 4-[N-methyl-N-(2-chloroethyl)amino]benzyl-5'-phosphamido derivative of heptanucleotide pd[CCAAACA]. Its melting temperature was shown to be 70 degrees C. Tm did not depend on covalent adduct concentration and was by 40 degrees C higher than that for unmodified duplex pd[TGTTTGGC].pd[CCAAACA] at concentration of 0.5 x 10(-4) M. The spatial structure of the covalent adduct in aqueous solution was investigated by two-dimensional 3H-NMR spectroscopy. The assignment of oligonucleotide protons as well as protons of a modifying group was carried out using COSY, COSY-DQF and NOESY experiments. Conformational analysis of proton-proton coupling constants for H1', H2'a, H2'b and H3' protons showed the sugar residues to be in 2'-endo conformation. Analysis of NOE connectivities observed between the protons of the alkylating group and oligonucleotide protons yielded conclusion, regarding the 4-[N-methyl-N-(2-chloroethyl)amino]benzylamido 5'-residue being localized in the region of the lacked nucleoside residue of the heptanucleotide chain about 5 A apart from the dC-1 residue and from cytosine base of the alkylated dC-8 residue.
authors.forename: E V
authors.initials: EV
authors.lastname: Bichenkova
authors.forename: T V
authors.initials: TV
authors.lastname: Mal'tseva
authors.forename: T V
authors.initials: TV
authors.lastname: Abramova
authors.forename: A V
authors.initials: AV
authors.lastname: Lebedev
mesh_terms: D000478:Alkylation; D001483:Base Sequence; D004591:Electrophoresis, Polyacrylamide Gel; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D009841:Oligonucleotides / Q000737:chemistry*; D011522:Protons; D012996:Solutions; D014867:Water / Q000737:chemistry
chemical_list: D009841:Oligonucleotides; D011522:Protons; D012996:Solutions; D014867:Water
vernacular_title: Vnutrikompleksnoe alkilirovanie oktanukleotida pd(TGTTTGGC) 5'-(4-N-methyl-N-(2-chlorétil)-amino)benzilfosfamidnym proizvodnym geptanukeltodia pd(CCAAACA). Poluchenie kovalentnogo addukta i issledovanie ego prostranstvennoĭ struktury v vodnom rastvore metodom dvumernoĭ (1)H-IaMR-spektroskopii.