A β-Boronopeptide Bundle of Known Structure As a Vehicle for Polyol Recognition

Abstract

Despite significant progress in the design of receptors and sensors for simple polyols and monosaccharides, few synthetic receptors discriminate among multiple saccharide units simultaneously, especially under physiological conditions. Described here is the three-dimensional structure of a supramolecular complex-a β-peptide bundle-designed for the potential to interact simultaneously with as many as eight discrete monosaccharide units. The preliminary evaluation of this construct as a vehicle for polyol binding is also presented.

Boronic Acid‐Based Carbohydrate Sensing

“…Schepartz and co‐workers introduced a β‐boronopeptide bundle with the unique property of being able to interact with different kinds of monosaccharides simultaneously . As shown in Figure , the boronic acid moiety was introduced on the outside surface of a β‐peptide through a palladium‐catalyzed borylation reaction.…”

“…Schepartz and co-workers introduced a b-boronopeptide bundle with the unique property of being able to interact with differentk indso fm onosaccharides simultaneously. [35] As shown in Figure 8, the boronic acid moiety was introduced on the outside surface of a b-peptide through ap alladium-catalyzed borylationr eaction. Isothermal titrationc alorimetry (ITC) showedt hat this modified peptide was able to bind to polyol metabolites such as dopamine and sorbitol in neutral solution.…”

The binding of boronated peptides to low affinity mammalian saccharides

“…Isothermal titration calorimetry (ITC) can be a very accurate and sensitive method for the measurement of the strength of molecular interactions, and boronic acid researchers have recently begun to apply the technique to boronate ester formation . Isothermal titration calorimetry has the added advantage of allowing the dissection of the Gibb's free energy of binding into enthalpic and entropic contributions.…”

“…Amongst the receptors that use covalent interactions, boronic acid‐containing compounds have been the most extensively explored because of their ability to rapidly and reversibly associate with 1,2‐ and 1,3‐diol functionalities present on many sugars . Borono‐lectins or boronic acid‐containing compounds designed to be small molecule mimics of lectins, are now receiving heightened interest from molecular recognition researchers …”

“…Schepartz et al described boronated dodecameric β‐peptides that form octameric bundles in which the boronic acid functionalities are solvent exposed . Despite the use of borono phenylalanine, which as indicated above, would not normally be expected to strongly associate with sugars at physiological pH, the judicious insertion of cationic amino acid side chains following structure‐guided design produced boronated β‐peptide bundles that were able to bind fructose in neutral water .…”