Dynamic Combinatorial Chemistry: Lysozyme Selects an Aromatic Motif That Mimics a Carbohydrate Residue

Direct Composition Analysis of a Dynamic Library of Imines in an Aqueous Medium

“…), a significant amplification of the peaks corresponding to imines A·1 and A·2 was observed (Figure 1c). [7,8] This supports our previous experiments with a reductive treatment of the library, [5] in which amine A1, resulting from A·1 reduction, had been shown to be amplified by lysozyme. The addition of more lysozyme (2 more equiv.)…”

“…[12] This type of analysis also revealed that the reduction step used in our previous DCL experiments [5] and presumably in the others [2] is slow enough so that the equilibrating DCL of imines is not perturbed. When sodium cyanoborohydride was added to the above experiments, the imine and the resulting amine concentrations were accessible on the same chromatogram; hence, the rate of amine formation could be followed with time (see Figure 2 for imine A·1 and amine A1).…”

“…In a recent article, [5] we have shown that hen egg white lysozyme (HEWL) is able to select an inhibitor from a library of imines obtained by the reaction of monosaccharide derived amines with a series of aromatic aldehydes. In these imines, the aromatic moiety is presumed to mimic a second carbohydrate unit that interacts with the enzyme's binding site.…”

Dynamic Combinatorial Chemistry: Ligands for Biomolecules

“…Consequently, although DCC has only been developed during a relatively short period of time, its potential in biological systems has been demonstrated in a number of examples (Table 5.2 ). cyclin -dependent kinase 2 hydrazone exchange ND oxindole structures [28] Aurora kinase thiol -disulfi de exchange ND 3 -amidobenzamide structure [29] glutathione S -transferase conjugate addition 5 glutathione derivatives [30] glutathione S -transferase conjugate addition ND inhibitors [31] neuraminidase transimination > 40000 Tamifl u analogs [32] neuraminidase transimination ND Tamifl u analogs [33] hen egg white lysozyme transimination 6 N -acetylglucosamine derivative [34] hen egg white lysozyme transimination 12 N -acetylglucosamine derivative [35] P. cepacia lipase nitroaldol reaction 16 β -nitroacetates [36] galactosyl transferase transimination ND UDP -galactose mimics [37] galactosyl transferase transimination ND UDP -galactose mimics [38] subtilisin thiol -disulfi de exchange 3 thiocolchicine/ podophyllotoxin conjugates [39] β -lactamase thiol -disulfi de exchange ND N -benzoyl -D -cysteine [40] other proteins anti -β -endorphin transamidation ND peptides [41] 5. As can be seen from Table 5.2 , nearly all different classes of biomolecules have been targeted, including enzymes and receptor proteins, oligonucleotides, and whole cells, and libraries have also been constructed using a range of different building blocks.…”

Dynamic Combinatorial Diversity in Drug Discovery

“…The corresponding amine was analyzed by HPLC after reduction with sodium cyanoborhydride. neuraminidase [26,27] and hen egg white lysozyme (HEWL) [58]. In the former case, a dynamic imine library was generated from eight different aldehydes and 4-hydroxypiperidine, and resulted in the preliminary identification of two amines that showed inhibitory activity after the reductive step.…”