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1 H NMR Characterization of Methacrylamide Polymer Conjugates with the Anti‐Cancer Drug Doxorubicin
Author(s) -
Pinciroli V.,
Rizzo V.,
Angelucci F.,
Tatò M.,
Vigevani A.
Publication year - 1997
Publication title -
magnetic resonance in chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.483
H-Index - 72
eISSN - 1097-458X
pISSN - 0749-1581
DOI - 10.1002/(sici)1097-458x(199701)35:1<2::aid-omr24>3.0.co;2-d
Subject(s) - chemistry , pyranose , methacrylamide , polymer , nmr spectra database , two dimensional nuclear magnetic resonance spectroscopy , nuclear magnetic resonance spectroscopy , stereochemistry , side chain , proton nmr , conjugate , molecule , monomer , combinatorial chemistry , organic chemistry , spectral line , acrylamide , mathematical analysis , physics , mathematics , astronomy
Abstract Two poly‐2‐hydroxypropylmethacrylamide conjugates with the anti‐cancer drug doxorubicin were investigated by 1 H NMR spectroscopy. In both polymers (FCE 28068 and FCE 28069) the drug is connected to a polymethacrylamide backbone via a tetrapeptidyl spacer (Gly‐ L , D ‐Phe– L ‐Leu–Gly) and, in addition, FCE 28069 contains similarly bound D ‐galactosamine molecules as liver‐targeting moieties. Signals of the drug and galactosamine protons were fully assigned in the spectra of the polymers by means of NOESY and TOCSY experiments and by comparison with the spectra of reference compounds. The integrity of doxorubicin and the connectivity between the drug and peptidyl chain was successfully confirmed in spite of the comparatively low abundance (<5%) of the corresponding monomeric units and of signal spreading due to the diastereomeric mixture of peptidyl chains. Polymer‐bound galactosamine molecules were found to be distributed among four isomeric forms (α‐ and β‐anomers of pyranose and furanose forms, with predominance of the α‐pyranose form). Diagnostic signals for possible alternative peptidyl chain endings (2‐hydroxypropylamide or free carboxyl groups) were identified with the help of model polymers and the first, but not the second, were detected in the spectra of the two FCEs. In addition to the above results, high‐field NMR is a rapid and sensitive method for the qualitative identification of low molecular weight contaminants in production batches of polymer–drug conjugates. © 1997 by John Wiley & Sons, Ltd.