High‐Affinity Disaccharide Binding by Tricyclic Synthetic Lectins

Abstract

Stay flexible: Rigid preorganization is not always the best approach to molecular recognition. Unlike previous synthetic lectins, new receptors (see picture) were synthesized that possess conformational freedom which allows hydrophobically driven collapse of the cavity. Nonetheless, they bind their carbohydrate targets in water with ground‐breaking affinities (up to 4500 M−1 for methyl cellobioside, R=Me) and selectivities.

Synthetic bacteriochlorins bearing polar motifs (carboxylate, phosphonate, ammonium and a short PEG). Water-solubilization, bioconjugation, and photophysical properties

“…31 P NMR (162 MHz) chemical shifts are reported for the sample in CDCl 3 versus the resonance of phosphoric acid (H 3 PO 4 ) as an external reference (insert tube). Known compounds 1a, 45 2a, 47 1-Bromo-3,5-bis(bromomethyl)benzene (1a). MALDI-MS was performed with the matrix 1,4bis(5-phenyl-2-oxaxol-2-yl)benzene (POPOP) for bacteriochlorins, 64 except that a-cyano-4-hydroxycinnamic acid (CHCA) was used for BC5.…”

“…3,5-bis(aminomethyl)bromobenzene 2a (derived from 1a) 47 with bis(pinacolato)diboron gave the Boc-protected Suzuki coupling partner 2 in 79% yield. The Suzuki coupling reactions were carried out with the palladium dichloride reagent containing a 1,1 0 -bis(diphenylphosphino)ferrocene (dppf) ligand in the presence of dimethylsulfoxide (DMSO).…”

Hydrophilic Oligo(lactic acid)s Captured by a Hydrophobic Polyaromatic Cavity in Water

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Biologically relevant hydrophilic molecules rarely interact with hydrophobic compounds and surfaces in water owingt oe ffective hydration. [3] We recently found by chance that molecular capsule 1 (Figure 1b), [4] which has ahydrophobic cavity fully surrounded by multiple polyaromatic panels,e nables the selective encapsulation of hydrophilic and water-stable d-sucrose from am ixture of natural disaccharides in water. X-rayc rystallographic and ITC analyses revealed that the unusual host-guest behavior is caused by enthalpic stabilization through multiple CH-p and hydrogen-bonding interactions.T he polyaromatic cavity stabilizes hydrolyzable cyclic di(lactic acid) and captures tetra(lactic acid) preferentially from am ixture of oligo(lactic acid)s even in water.

Hydrophilicity and hydrophobicity are essentially incompatible so that biologically relevant hydrophilic molecules and oligomers rarely interact with hydrophobic molecules, surfaces,a nd pockets.

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“…[1] There are al arge number of reports on molecular cages and capsules possessing hydrophobic cavities to efficiently bind hydrophobic molecules in water, predominantly through hydrophobic effects. [3] We recently found by chance that molecular capsule 1 (Figure 1b), [4] which has ahydrophobic cavity fully surrounded by multiple polyaromatic panels,e nables the selective encapsulation of hydrophilic and water-stable d-sucrose from am ixture of natural disaccharides in water. [3] We recently found by chance that molecular capsule 1 (Figure 1b), [4] which has ahydrophobic cavity fully surrounded by multiple polyaromatic panels,e nables the selective encapsulation of hydrophilic and water-stable d-sucrose from am ixture of natural disaccharides in water.…”

“…[2] However, hydrophilic bio-oligomers comprising,f or example,a mino acids with polar side chains,nucleic acids,and saccharides are entirely hydrated in water (Figure 1a,l eft), and thus most previously reported hydrophobic cavities hardly or weakly interact with these substrates in aqueous media. [3] We recently found by chance that molecular capsule 1 (Figure 1b), [4] which has ahydrophobic cavity fully surrounded by multiple polyaromatic panels,e nables the selective encapsulation of hydrophilic and water-stable d-sucrose from am ixture of natural disaccharides in water. [5] This unusual finding stimulated us to explore the host capability of 1 toward hydrophilic and labile biologically relevant oligomers,o ligo(lactic acid)s, which so far could not be bound by previously developed synthetic cages and capsules in water.…”