Three-point binding

Figure 10.8 Three-point binding model for prediction of NeuA stereoselectivity based on conformational analysis.

Because of the tetrahedral stereocenter of the amino acid, three-point binding can occur with proper alignment for only one of the two enantiomers. 

Figure 5.7 Only one of the two amino acid enantiomers shown can achieve three-point binding with the hypothetical binding site (e.g., in an enzyme). 

After finalization of this review, an independent mechanistic model for NeuA catalysis has been proposed (Fitz, W, Schwark, J-R, Wong, C-H (1995) J Org Chem 60 3663) which is based on consideration of products derived from additions to aldotetroses rather than our conformational analysis and rationalization of a three-point binding motif for the natural acceptor substrate (Sect. 3.1, Scheme 2). 

Figure 8 Model of substrate binding to protein lowing a proper three-point binding interaction (A) and of the enantiomer showing an improper three-point binding interaction (B). [Adapted from Christensen (8).]...

The two families of macrocyclic phosphine oxide disulfoxides (100 X = (CH2)2, 1,2-xylyl, 1,3-xylyl) and (101 X = (CH2)3 s, 1,2-xylyl, 1,3-xylyl) have been prepared stereoselectively for comparisons of three-point binding abilities with monoalkylammonium ions <92TL2107, 93PAC461, 93JA7900). Compound (101 X = 1,2-xylyl) also binds halide ions <94JA4069>. 

Nemeth. D. Rebek, J., Jr. Molecular recognition Three-point binding leads to a selective receptor for aromatic... 

A useful concept for chiral separation using a transport or extraction reagent is the three-point binding rule developed for chiral chromatography. The rule states that a minimum of three simultaneous interactions between the chiral stationary phase and one of the enantiomers are necessary to achieve enantioselection, with at least one of these interactions being stereochemically dependent. We describe chiral guanidiniums that apply this rule in the recognition, extraction, or transport separation of amino acids and peptides. 

Figure 7 Triboronic acid sensors assembled via combinatorial synthesis to evaluate the potential of increased allosteric binding effects through three-point binding (the interchangeable linker units are highlighted in red).

This three point binding mode implies that the chirality of the helix determines the asymmetric induction of the epoxidation and not the chirality of the or-carbon atoms of the peptide catalyst. " Natural enzymes show related arrangements of three NHs as binding motif for fully or partially negatively charged entities. The oxy-anion hole in serine esterase is known to use a similar H-bonding motif as proposed in this model. ... 

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