title: High fidelity kinetic self-sorting in multi-component systems based on guests with multiple binding epitopes.
abstract: The molecular recognition platforms of natural systems often possess multiple binding epitopes, each of which has programmed functional consequences. We report the dynamic behavior of a system comprising CB[6], CB[7], and guests cyclohexanediammonium (1) and adamantanealkylammonium (2) that we refer to as a two-faced guest because it contains two distinct binding epitopes. We find that the presence of the two-faced guest--just as is observed for protein targeting in vivo--dictates the kinetic pathway that the system follows toward equilibrium. The influence of two-faced guest structure, cation concentration, cation identity, and individual rate and equilibrium constants on the behavior of the system was explored by a combination of experiment and simulation. Deconstruction of this system led to the discovery of an anomalous host-guest complex (CB[6].1) whose dissociation rate constant (k(out) = 8.5 x 10(-10) s(-1)) is approximately 100-fold slower than the widely used avidin.biotin affinity pair. This result, in combination with the analysis of previous systems which uncovered extraordinarily tight binding events (K(a) > or = 10(12) M(-1)), highlights the inherent potential of pursuing a systems approach toward supramolecular chemistry.
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742, USA.
authors.forename: Pritam
authors.initials: P
authors.lastname: Mukhopadhyay
authors.forename: Peter Y
authors.initials: PY
authors.lastname: Zavalij
authors.forename: Lyle
authors.initials: L
authors.lastname: Isaacs
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D000939:Epitopes / Q000737:chemistry*; D007700:Kinetics; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D013816:Thermodynamics
chemical_list: D000939:Epitopes