Understanding structural/functional properties of immunoconjugates for cancer therapy by computational approaches

Caterina Arcangeli, Cristina Cantale, Patrizia Galeffi, Giulio Gianese, Raffaella Paparcone, Vittorio Rosato

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11 Citations (Scopus)


Monoclonal antibodies coupled to highly toxic molecules (immunoconjugates) are currently being developed for cancer therapy. We have used an in silico procedure for evaluating some physicochemical properties of two tumor-targeting anti-HER2 immunoconjugates: (a) the single-chain antibody scFv(FRP5) linked to a bacterial toxin, that has been recently progressed to phase I clinical trial in human cancer; (b) the putative molecule formed by the intrinsically stable scFv(800E6), which has been proposed as toxin carrier to cancer cells in human therapy, joined to the same toxin of (a). Structural models of the immuno-conjugates have been built by homology modeling and assessed by molecular dynamics simulations. The trajectories have been analyzed to extract some biochemical properties and to assess the potential effects of the toxin on the structure and dynamics of the anti-HER2 antibodies. The results of the computational approach indicate that the antibodies maintain their correct folding even in presence of the toxin, whereas a certain stiffness in correspondence of some structural regions is observed. Furthermore, the toxin does not seem to affect the antibody solubility, whereas it enhances the structural stability. The proposed computational approach represent a promising tool for analyzing some physicochemical properties of immunoconjugates and for predicting the effects of the linked toxin on structure, dynamics, and functionality of the antibodies. © 2008 Taylor & Francis Group, LLC.
Original languageEnglish
Pages (from-to)35 - 47
Number of pages13
JournalJournal of Biomolecular Structure and Dynamics
Issue number1
Publication statusPublished - 2008
Externally publishedYes


All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

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