Design of Hetero-Bivalent Polypeptides as Kinetics-Based Sensors for High-Sensitivity Detection of Weak Molecular Interactions

摘要

Multivalent molecular interactions found throughout biological systems provide stable high-affinity complexes by increasing the statistical probability of re-binding of constituent binding moieties to the receptor sites at supramolecular surfaces [1] and in solution [2]. Not only its thermodynamic stability, kinetics behavior of the multivalent system is also important. Transient exposure of unoccupied binding sites, which ocuurs in the course of stepwise dissociation of the multivalent complex, allows for fast displacement of high-affinity ligands with competing molecules [3]. To understand thermodynamic and kinetic aspects of dynamic control of naturally-occurring or artificially-designed multivalent protein inhibitors, a detailed analysis of molecular events accompanying the process of stepwise dissociation is required.