Monomers containing substrate or inhibitor residues for copper amine oxidases and their hydrophilic beaded resins designed for enzyme interaction studies

Bertini, Veronica; Alfei, Silvana; Pocci, Marco; Lucchesini, Francesco; Picci, Nevio; Iemma, Francesca

doi:10.1016/j.tet.2004.09.083

Cited by 19 publications

(32 citation statements)

References 33 publications

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“…19 The process followed in every aspect what was already observed. The obtained resin R2 had a loading of NH 2 groups ¼ 311 mmol g À1 .…”

Section: Resultsmentioning

confidence: 87%

“…Nevertheless, in a previous study, 19 we prepared the first soluble copolymers (P1a and P1c, Scheme 1) and resin (R1a, Scheme 1) containing aminoalkylbenzene residues, which were very good substrates of lysyl oxidase and BAO, with P1c also being active toward DAO. Interestingly, we found that R1a was as active toward lysyl oxidase as the natural substrate elastin, and P1c was 9.7 times more active than elastin itself.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and evaluation of resins bearing substrate-like inhibitor functions for capturing copper amine oxidases

Pocci

Alfei

Castellaro

et al. 2013

Polym J

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The aim of this work was to make new tools available for investigating the interactions between enzymes and substrate-like inhibitors in copper amine oxidases (CAOs), a class of enzymes that controls important cellular processes, such as the crosslinking of elastin and collagen, cell proliferation and the regulation of intracellular polyamines. Starting from previous work, we synthesized the poly(N,N-dimethylacrylamide)-based resin R2 and the new TentaGel resins T3 and T4 obtained by ether bonding CAO substrate-like inhibitor moieties onto commercial TentaGel S-Br, which contains bromomethyl groups susceptible to nucleophilic substitution reactions. We used polyacrylamide gel electrophoresis (PAGE) experiments to determine the capability of the prepared resins to capture plasma amine oxidase (PAO) and diamine oxidase (DAO), members of the CAO family. The poly(N,N-dimethylacrylamide)-based resin R2 was able to block PAO and DAO, being the first insoluble polymeric material capable of capturing enzymes of the CAO family. Keywords: copper amine oxidases; 2,6-dialkoxybenzylamines; electrophoresis; functionalization; tentagel resins INTRODUCTIONCopper amine oxidases (CAOs, EC 1.4.3.6) are ubiquitous enzymes found in prokaryotes and eukaryotes, humans included, where they control important cellular processes, such as the crosslinking of elastin and collagen, cell proliferation and the regulation of intracellular polyamines. With the exception of lysyl oxidase (32 kDa), CAOs are homodimers with subunit molecular weights between 70 kDa and 95 kDa, and with one copper ion and a quinone cofactor per subunit. CAOs are also characterized by the presence of cysteine residues and a variable percentage of carbohydrates, depending on the enzyme source.The enzymatic reaction results in the deamination of aminomethyl substrates to produce aldehydes, ammonia and reduced molecular oxygen in the form of hydrogen peroxide.Knowledge concerning the physiological role, mechanism of action 1-4 and numerous X-ray structures 5-14 of these enzymes, as well as methods for protein expression of CAOs, 15 making larger quantities of protein samples available, which is useful for various experiments, has grown progressively in the past two decades.Remarkably, one of the X-ray structures indicates that the complex between 2-hydrazinopyridine, a non-substrate-like, nonselective, carbonyl group scavenger inhibitor, and Escherichia coli amine oxidase results in the formation of an imine double bond between the NH 2 of the inhibitor and the C-5 carbonyl group of the cofactor 2,4,5-trihydroxyphenylalanine quinone. 16

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“…19 The process followed in every aspect what was already observed. The obtained resin R2 had a loading of NH 2 groups ¼ 311 mmol g À1 .…”

Section: Resultsmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Synthesis and evaluation of resins bearing substrate-like inhibitor functions for capturing copper amine oxidases

Pocci

Alfei

Castellaro

et al. 2013

Polym J

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“…N-(4-Vinylbenzoyl)-6-amino-6-deoxy-1,2,3,4-tetra-O-acetyl-Dgalactose (4). A solution of 1abpf 21 (2.56 g, 8.3 mmol) in dry pyridine (10 mL) was cooled to 0 C, treated under N 2 with acetic anhydride (4.51 g, 44.1 mmol, 4.2 mL), le 24 h under N 2 and magnetic stirring at room temperature, then hydrolyzed with water (20 mL, pH ¼ 6-7) and extracted with CH 2 Cl 2 (3 Â 20 mL).…”

Section: Methodsmentioning

confidence: 99%

Synthesis, glycosylation and NMR characterization of linear peracetylated d-galactose glycopolymers

et al. 2015

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The glycosylation of D-galactose glycopolymers to produce functionalized polymers expected to be bioactive as substrates or inhibitors of enzymes of the copper amine oxidase class (CAOs, EC 1.4.3.6), attained previously with an unpractical, but significant process requesting a large excess of glycosyl acceptor, has now been achieved with a method based on the use of peracetylated D-galactose moieties, in the presence of SnCl 4 or BF 3 $Et 2 O as promoters, which employs glycosyl donors in nearly stoichiometric ratio with the desired glycosyl acceptor. After the synthesis of an appropriate model molecule acting as a guide, the new method was set up with extensive NMR investigations on the same model molecule and soluble polymeric reagents and products, performing a full rationalization of the chemical behavior of the various a and b pyranose and furanose forms of D-galactose residues.Glycosylated systems containing functionalities protected with trifluoroacetyl and acetyl groups were fully deprotected in one step through a reduction procedure with NaBH 4 . ; Fax: +39 010 3532684; Tel: +39 010 3532685 † Electronic supplementary information (ESI) available: Homopolymerization data of 4; glycosylation data of 5; molecular formulas with numbering of the carbons of 4abp, 4abf, 5abp, 5abf, 7bf, 9bp, and 10abp for NMR assignments; characterization of compounds 7abf, 8, 9bp, and 10abp; 1 H and 13 C NMR spectra of 4ap, 4bp, 5ap, 5bp, 6ap, 6bp, 7abf, 8, 9bp, 10abp, 11 and 12. See Chart 1 D-Galactose styrene monomer 1abpf, N-protected glycosyl acceptor 2, and model molecule 3abpf. 23836 | RSC Adv., 2015, 5, 23835-23846 This journal is

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“…PZLLys macromonomer was synthesized by ROP of NCA monomer23 with 4‐VBA HCl as the initiator 24. 4‐VBA HCl was obtained from Gabriel synthesis as described in the literature 25…”

Section: Methodsmentioning

confidence: 99%

Synthesis and characterization of pH‐sensitive and thermosensitive double hydrophilic graft copolymers

Wang

Chen

2011

J. Polym. Sci. A Polym. Chem.

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A series of poly(N‐isopropylacrylamide)‐co‐poly(Nε‐benzyloxycarbonyl‐L‐lysine) graft copolymers (PNIPAm‐co‐PZLLys) with different side chains (degree of polymerization, DP = 5∼40) and unit ratios (from 30 to 70 mol %) were prepared via free radical polymerization, followed by cleaving benzyloxycarbonyl groups (Z groups) to obtain the double hydrophilic graft copolymer, poly(N‐isopropylacrylamide)‐co‐poly(L‐lysine) (PNIPAm‐co‐PLLys). The pH‐ and temperature‐response properties of the graft copolymers in aqueous solution were studied. The experimental results indicate L15‐N30 and L15N‐70, that is, the PNIPAm‐co‐PLLys having the poly(L‐lysine) of DP = 15 as side chains as well as 30 and 70 mol %, respectively, of PNIPAm as backbone, have coil‐to‐helix transitions from pH 6 to pH 12 at room temperature and form uniform nanoscale micelle‐like dispersions in aqueous solution at pH 12. The graft copolymers also could form uniform and nanoscale micelle‐like structures at 50 °C in pH 6 buffer solution due to slightly polymer aggregation. With temperature and pH increased, both the deprotonated PLLys side chains and PNIPAm backbone become hydrophobic, leading to polymer precipitation. These results illustrate that a double tunable hydrophilic graft copolymer had been successfully synthesized via a simple radical polymerization, and could form micelles without serious polymer aggregation at a lower pH and a higher temperature. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011

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Monomers containing substrate or inhibitor residues for copper amine oxidases and their hydrophilic beaded resins designed for enzyme interaction studies

Cited by 19 publications

References 33 publications

Synthesis and evaluation of resins bearing substrate-like inhibitor functions for capturing copper amine oxidases

Synthesis and evaluation of resins bearing substrate-like inhibitor functions for capturing copper amine oxidases

Synthesis, glycosylation and NMR characterization of linear peracetylated d-galactose glycopolymers

Synthesis and characterization of pH‐sensitive and thermosensitive double hydrophilic graft copolymers

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