Dynamic force spectroscopy of parallel individual mucin1-antibody bonds

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We used atomic force microscopy (AFM) to measure the binding forces between Mucin1 (MUC1) peptide and a single chain antibody fragment (scFv) selected from a scFv library screened against MUC1. This binding interaction is central to the design of the molecules for targeted delivery of radioimmunotherapeutic agents for prostate and breast cancer treatment. Our experiments separated the specific binding interaction from non-specific interactions by tethering the antibody and MUC1 molecules to the AFM tip and sample surface with flexible polymer spacers. Rupture force magnitude and elastic characteristics of the spacers allowed identification of the bond rupture events corresponding to different ... continued below

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Sulchek, T A; Friddle, R W; Langry, K; Lau, E; Albrecht, H; Ratto, T et al. May 2, 2005.

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We used atomic force microscopy (AFM) to measure the binding forces between Mucin1 (MUC1) peptide and a single chain antibody fragment (scFv) selected from a scFv library screened against MUC1. This binding interaction is central to the design of the molecules for targeted delivery of radioimmunotherapeutic agents for prostate and breast cancer treatment. Our experiments separated the specific binding interaction from non-specific interactions by tethering the antibody and MUC1 molecules to the AFM tip and sample surface with flexible polymer spacers. Rupture force magnitude and elastic characteristics of the spacers allowed identification of the bond rupture events corresponding to different number of interacting proteins. We used dynamic force spectroscopy to estimate the intermolecular potential widths and equivalent thermodynamic off rates for mono-, bi-, and tri-valent interactions. Measured interaction potential parameters agree with the results of molecular docking simulation. Our results demonstrate that an increase of the interaction valency leads to a precipitous decline in the dissociation rate. Binding forces measured for mono and multivalent interactions match the predictions of a Markovian model for the strength of multiple uncorrelated bonds in parallel configuration. Our approach is promising for comparison of the specific effects of molecular modifications as well as for determination of the best configuration of antibody-based multivalent targeting agents.

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PDF-file: 30 pages; size: 0.5 Mbytes

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  • Journal Name: Proceedings of the National Academy of Sciences USA; Journal Volume: 102

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  • Report No.: UCRL-JRNL-214131
  • Grant Number: W-7405-ENG-48
  • Office of Scientific & Technical Information Report Number: 878199
  • Archival Resource Key: ark:/67531/metadc877159

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Office of Scientific & Technical Information Technical Reports

Reports, articles and other documents harvested from the Office of Scientific and Technical Information.

Office of Scientific and Technical Information (OSTI) is the Department of Energy (DOE) office that collects, preserves, and disseminates DOE-sponsored research and development (R&D) results that are the outcomes of R&D projects or other funded activities at DOE labs and facilities nationwide and grantees at universities and other institutions.

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  • May 2, 2005

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  • Sept. 21, 2016, 2:29 a.m.

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  • Dec. 5, 2016, 2:31 p.m.

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Sulchek, T A; Friddle, R W; Langry, K; Lau, E; Albrecht, H; Ratto, T et al. Dynamic force spectroscopy of parallel individual mucin1-antibody bonds, article, May 2, 2005; Livermore, California. (digital.library.unt.edu/ark:/67531/metadc877159/: accessed December 18, 2018), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT Libraries Government Documents Department.