Disease relevance of boronic acid

• The proteasome inhibitor bortezomib (also known as PS-341/Velcade) is a dipeptidyl boronic acid that has recently been approved for use in patients with multiple myeloma [1].
• By utilizing HIV-1 Tat, as well as ProboroPro, a potent and specific boronic acid analog inhibitor of DP IV, we show here that blocking DP IV partially inactivates Ag and anti-CD3-mediated T cell proliferation [2].
• Hepatitis C virus NS3 protease requires its NS4A cofactor peptide for optimal binding of a boronic acid inhibitor as shown by NMR [3].
• Crystal structure of Escherichia coli penicillin-binding protein 5 bound to a tripeptide boronic acid inhibitor: a role for Ser-110 in deacylation [4].
• Crystal structure of Enterobacter cloacae 908R class C beta-lactamase bound to iodo-acetamido-phenyl boronic acid, a transition-state analogue [5].

High impact information on boronic acid

• Given their affinity and specificity for arginase, boronic acid inhibitors are especially useful for probing the role of arginase in living systems [6].
• The structure of the plasmid-mediated beta-lactamase TEM-1 has been solved in complex with a designed boronic acid inhibitor (1R)-1-acetamido-2-(3-carboxyphenyl)ethane boronic acid at 1.7 A resolution [7].
• Lastly, we synthesized two boronic acid transition state analogs that mimic cephalothin and found substitutions at Arg-244 markedly affect both the affinity and kinetics of binding to the chiral, deacylation transition state inhibitor [8].
• The nonenzymatic glycation of glomerular basement membranes (GBMs) from 14 diabetic and 19 nondiabetic human subjects was determined after boronic acid affinity and high-performance cation-exchange chromatography of their NaB[3H]4-reduced ketoamine adducts [9].
• The amount of nonenzymatic glycosylation present in normal and diabetic rat peripheral nerve myelin, whole brain, brain myelin, and individual myelin protein components was determined using NaB3H4 reduction followed by either boronic acid affinity chromatography or SDS-polyacrylamide gel electrophoresis (SDS-PAGE) [10].

Chemical compound and disease context of boronic acid

• The structure of the complex formed between alpha-lytic protease, a serine protease secreted by Lysobacter enzymogenes, and N-tert-butyloxycarbonylalanylprolylvaline boronic acid (Ki = 0.35 nM) has been studied by X-ray crystallography to a resolution of 2.0 A [11].

Biological context of boronic acid

• The boronic acid binding site on lipase is at or near the active center serine since modification of this residue by diethyl p-nitrophenyl phosphate was prevented by boronic acids [12].
• Moreover, the previously postulated structure of the tetrahedral intermediate for substrate hydrolysis is isosteric with these boronic acid adducts, which can therefore be considered good models for the transition state complex (KOEHLER, K.K., and LIENHARD, G.E. (1972) Biochemistry 10, 2477-2483) [13].
• In the current investigation, we determine the regio- and stereochemical features of the various equilibrating sugar isomers that induce signal transduction in boronic acid chemosensors such as 1 as well as 2 and 3 [14].
• Affinity electrophoresis for monitoring terminal phosphorylation and the presence of queuosine in RNA. Application of polyacrylamide containing a covalently bound boronic acid [15].
• Structure-activity relationships of boronic acid inhibitors of dipeptidyl peptidase IV. 1. Variation of the P2 position of Xaa-boroPro dipeptides [16].

Anatomical context of boronic acid

• We demonstrate that the cis-6 boronic acid bioisostere of CA-4: (1) inhibits tubulin assembly, (2) competitively displaces colchicine, and (3) is a low-nanomolar inhibitor of human cancer cell lines [17].
• Here we show that three high-affinity inhibitors of furin efficiently blocked killing of murine J774A.1 macrophages by recombinant protective antigen plus lethal factor: RRD-eglin and RRDG-eglin, developed by engineering the protein protease inhibitor eglin c, and the peptide boronic acid inhibitor acetyl-Arg-Glu-Lys-boroArg pinanediol [18].
• Characterization of peptidyl boronic acid inhibitors of mammalian 20 S and 26 S proteasomes and their inhibition of proteasomes in cultured cells [19].
• We have designed and synthesized a highly lipophilic boronic acid (11) with a molecular shape that makes it much more effective at carrying sugars through organic membranes than a previously used steroidal boronic acid [20].
• Boronic acid was introduced in the polymer as recognition site of sugar residues existing on the plasma membrane surface of lymphocyte, since it makes a covalent bonding with polyol compounds including sugars [21].

Associations of boronic acid with other chemical compounds

• The crystal structure of the complex between the binuclear manganese metalloenzyme arginase and the boronic acid analog of L-arginine, 2(S)-amino-6-boronohexanoic acid (ABH), has been determined at 1.7 A resolution from a crystal perfectly twinned by hemihedry [22].
• Polyadenosine- and adenosine-diphosphoribosylated proteins of hamster liver were quantitatively isolated with the aid of m-aminophenyl boronic acid glutaryl hydrazide polyacrylamide affinity resin by selective adsorption at pH 8.2 and elution at pH 4 [23].
• Affinity chromatography based on the complex formation of the modified nucleoside Q with boronic acid has been applied to the isolation of specific tRNA precursors containing this modified nucleoside [24].
• PS-341, a novel boronic acid dipeptide that inhibits 26S proteasome activity, has prominent effects in vitro and in vivo against several solid tumors [25].
• To address questions regarding the mechanism of serine protease catalysis, we have solved two X-ray crystal structures of alpha-lytic protease (alphaLP) that mimic aspects of the transition states: alphaLP at pH 5 (0.82 A resolution) and alphaLP bound to the peptidyl boronic acid inhibitor, MeOSuc-Ala-Ala-Pro-boroVal (0.90 A resolution) [26].

Gene context of boronic acid

• Transition state analogue boronic acid inhibitors mimicking the structures and interactions of good penicillin substrates for the TEM-1 beta-lactamase of Escherchia coli were designed using graphic analyses based on the enzyme's 1.7 A crystallographic structure [27].
• To our knowledge, this is the first report on P450-mediated drug-drug interaction potential of proteasome inhibitors or boronic acid containing therapeutics [28].
• The X-ray crystal structure of a fully active, truncated form of human arginase II complexed with a boronic acid transition state analogue inhibitor has been determined at 2.7 A resolution [29].
• Inhibition of dipeptidyl peptidase IV (CD26) by peptide boronic acid dipeptides [30].
• 2.4 A resolution crystal structure of the prototypical hormone-processing protease Kex2 in complex with an Ala-Lys-Arg boronic acid inhibitor [31].

Analytical, diagnostic and therapeutic context of boronic acid

• In order to isolate the 3H-labeled glycosylated peptides, the soluble tryptic peptide fraction was first subjected to boronic acid affinity chromatography [32].
• Glycated Cu,Zn-SOD, which binds to a boronic acid affinity column, was measured by the enzyme-linked immunosorbent assay [33].
• We compare the response of the boronic acid probes in the contact lens to solution-based measurements and can conclude that both the pH and polarity within the contact lens need to be considered with respect to choosing/designing and optimizing glucose-sensing probes for contact lenses [34].
• The resulting mixture, spiked with an internal standard, was treated by phenyl boronic acid column extraction, followed by reverse-phase high-performance liquid chromatography analysis [35].
• The structures of the class C beta-lactamase from Enterobacter cloacae 908R alone and in complex with a boronic acid transition-state analogue were determined by X-ray crystallography at 2.1 and 2.3 A, respectively [5].

References