Non-covalent carriage of anticancer agents by humanized antibody trastuzumab

J Mol Model. 2016 May;22(5):112. doi: 10.1007/s00894-016-2986-0. Epub 2016 Apr 25.

Abstract

This article explores the internalization and non-covalent carriage of small molecule anticancer agents like vinca alkaloids by humanized monoclonal antibody trastuzumab. Such carriage is marked by significant reduction in side effects and increased therapeutic value of these anticancer agents. This study is coherent with few clinical observations of enhanced efficiency of these anticancer agents when co-administered with therapeutic antibodies. This study will also serve as the foundation for screening a database of anticancer agents for possible compounds that may be co-delivered alongwith the antibody. Based on this study vincristine conformation inside antibody and its charge environment may be used as descriptors for screening purposes.

Keywords: Binding energy; MMGBSA; Molecular docking; Molecular dynamics; Monoclonal antibody; Non-covalent carriage; Simulation; Solvation free energy; Trastuzumab; Vinca alkaloid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Binding Sites
  • Drug Carriers / chemistry*
  • Humans
  • Hydrogen Bonding
  • Immunoglobulin Fab Fragments / chemistry
  • Molecular Docking Simulation
  • Mutation / genetics
  • Static Electricity
  • Thermodynamics
  • Trastuzumab / chemistry
  • Trastuzumab / pharmacology*
  • Vinblastine / analogs & derivatives
  • Vinblastine / chemistry
  • Vincristine / chemistry
  • Vinorelbine

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Immunoglobulin Fab Fragments
  • Vincristine
  • Vinblastine
  • Trastuzumab
  • Vinorelbine