Enhancing Binding Affinity by the Cooperativity between Host Conformation and Host–Guest Interactions

Abstract

Glutamate-functionalized oligocholate foldamers bound Zn(OAc)(2), guanidine, and even amine compounds with surprisingly high affinities. The conformational change of the hosts during binding was crucial to the enhanced binding affinity. The strongest cooperativity between the conformation and guest-binding occurred when the hosts were unfolded but near the folding-unfolding transition. These results suggest that high binding affinity in molecular recognition may be more easily obtained from large hosts capable of strong cooperative conformational changes instead of those with rigid, preorganized structures.

Allosteric and Chelate Cooperativity in Divalent Crown Ether/Ammonium Complexes with Strong Binding Enhancement

“…Together, these effects rationalize why such high positive chelate cooperativities, and together therewith unexpectedly high binding constants, are found, even though the guest spacers are flexible. This is in line with other examples questioning the commonly accepted notion that flexible chains that reduce binding interactions are scarce but do exist …”

Cooperatively Enhanced Receptors for Biomimetic Molecular Recognition

“…Because the corresponding methyl ester 4 and the parent hexacholate 5 ( Figure 3) displayed no FRET-enhanced dansyl emission with 0-30 % MeOH, the stronger folding of compound 3 should derive from its two glutamic-acid residues, most likely owing to the formation of an intramolecular carboxylic-acid dimer. [27] Interestingly, the binding between compound 3 and Zn(OAc) 2 was strongest in 15 % MeOH/EtOAc, right at the folding/unfolding transition (Figure 4 b). The immediate suggestion was that the conformation and guest binding of compound 3 were intimately related, with the strongest synergy near the folding/unfolding transition.…”

Oligocholate Foldamers as Carriers for Hydrophilic Molecules across Lipid Bilayers

“…According to the CPK model, the height of a fully folded 1 is about 1.7 nm, which is reasonably close to the hydrophobic thickness (1.95–2.09 nm) determined for the DLPC bilayer 32. Second, cholate hexamers fold well in the micelles of C 12 surfactants, such as SDS24 and Brij 35;15a this suggests that the dimensions of C 12 micelles and the folded cholate hexamers match quite well 33…”

“…23 Because methanol is completely miscible with ethyl acetate but nearly immiscible with hexane, a large amount of hexane in the mixture facilitates the phase separation of the methanol and helps the folding 10. 24…”