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Force spectroscopy of multivalent binding of riboflavin-conjugated dendrimers to riboflavin binding protein.

Abstract
Putative riboflavin receptors are considered as biomarkers due to their overexpression in breast and prostate cancers. Hence, these receptors can be potentially exploited for use in targeted drug delivery systems where dendrimer nanoparticles with multivalent ligand attachments can lead to greater specificity in cellular interactions. In this study, the single molecule force spectroscopy technique was used to assess the physical strength of multivalent interactions by employing a riboflavin (RF)-conjugated generation 5 PAMAM dendrimer G5(RF)n nanoparticle. By varying the average RF ligand valency (n = 0, 3, 5), the rupture force was measured between G5(RF)n and the riboflavin binding protein (RFBP). The rupture force increased when the valency of RF increased. We observed at the higher valency (n = 5) three binding events that increased in rupture force with increasing loading rate. Assuming a single energy barrier, the Bell-Evans model was used to determine the kinetic off-rate and barrier width for all binding interactions. The analysis of our results appears to indicate that multivalent interactions are resulting in changes to rupture force and kinetic off-rates.
AuthorsAbigail N Leistra, Jong Hyun Han, Shengzhuang Tang, Bradford G Orr, Mark M Banaszak Holl, Seok Ki Choi, Kumar Sinniah
JournalThe journal of physical chemistry. B (J Phys Chem B) Vol. 119 Issue 18 Pg. 5785-92 (May 07 2015) ISSN: 1520-5207 [Electronic] United States
PMID25872803 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Dendrimers
  • Membrane Transport Proteins
  • PAMAM Starburst
  • riboflavin-binding protein
  • Riboflavin
Topics
  • Calorimetry
  • Dendrimers (chemistry)
  • Kinetics
  • Membrane Transport Proteins (chemistry)
  • Microscopy, Atomic Force
  • Models, Molecular
  • Nanoparticles (chemistry)
  • Protein Binding
  • Riboflavin (chemistry)
  • Spectrum Analysis
  • Thermodynamics

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