The Experts below are selected from a list of 432 Experts worldwide ranked by ideXlab platform
David J Mooney - One of the best experts on this subject based on the ideXlab platform.
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degradable and injectable poly aldehyde Guluronate hydrogels for bone tissue engineering
Journal of Biomedical Materials Research, 2001Co-Authors: Kuen Yong Lee, Eben Alsberg, David J MooneyAbstract:Degradable and injectable hydrogels may be ideal for bone-tissue engineering, especially in the craniofacial region because of the ease of access for injection. Alginate hydrogels potentially could be used as injectable cell delivery vehicles, but they exhibit a limited range of mechanical properties and uncontrollable disintegration time. Therefore we synthesized new hydrogels, composed of poly(aldehyde Guluronate) (PAG) and adipic acid dihydrazide, that have a wide range of mechanical stiffness and controllable degradation rate. MC3T3-E1 cells adhered and multiplied on PAG hydrogels in vitro. When primary rat calvarial osteoblasts were mixed with PAG hydrogels and subcutaneously injected into the backs of mice, mineralized bone tissues were formed 9 weeks following implantation. These hydrogels may find wide utility as an injectable delivery system for bone precursor cells as well as for other applications in tissue engineering.
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sustained and controlled release of daunomycin from cross linked poly aldehyde Guluronate hydrogels
Journal of Pharmaceutical Sciences, 2000Co-Authors: Kamal H Bouhadir, Kuen Yong Lee, Geneveive M Kruger, David J MooneyAbstract:We have incorporated daunomycin, an antineoplastic agent, into a biodegradable hydrogel through a labile covalent bond. In brief, sodium alginate was chemically broken down to low molecular weight and followed by oxidation to prepare poly(aldehyde Guluronate). Adipic dihydrazide was used to incorporate the drug into the polymer backbone and cross-link the polymer to form hydrogels. Daunomycin can be released from the hydrogel after the hydrolysis of the covalent linkage between the drug and the polymer. A wide range of release profiles of daunomycin (e.g., from 2 days to 6 weeks) has been achieved using these materials, and the biological activity of the released daunomycin was maintained.
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degradation behavior of covalently cross linked poly aldehyde Guluronate hydrogels
Macromolecules, 2000Co-Authors: Kuen Yong Lee, Kamal H Bouhadir, David J MooneyAbstract:There is a significant need in the biomedical field for hydrogels with controllable mechanical and degradative properties. We now report the degradation behavior of novel hydrogels formed by the cr...
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synthesis of cross linked poly aldehyde Guluronate hydrogels
Polymer, 1999Co-Authors: Kamal H Bouhadir, Debra S Hausman, David J MooneyAbstract:Alginate is an attractive material for controlled drug delivery and cell transplantation applications. However, alginate hydrogels are not degradable, have limited mechanical properties, and lack the functional groups required for cell interaction. To address these limitations of alginate while maintaining their favorable characteristics, we have synthesized new polymers derived from sodium poly(Guluronate), the portion of the alginate molecule that is responsible for its gelling behaviour. Sodium poly(Guluronate) was isolated, oxidized with sodium periodate, and cross-linked with adipic dihydrazide to yield hydrogels with a wide range of mechanical properties, and with cell adhesion peptides coupled to their backbones.
Tsuyoshi Muramatsu - One of the best experts on this subject based on the ideXlab platform.
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crystal structure of the alginate poly alpha l Guluronate lyase from corynebacterium sp at 1 2 a resolution
Journal of Molecular Biology, 2005Co-Authors: Takuo Osawa, Tsuyoshi Muramatsu, Yasuhito Matsubara, Makoto Kimura, Yoshimitsu KakutaAbstract:The crystal structure of alginate (poly alpha-l-Guluronate) lyase from Corynebacterium sp. (ALY-1) was determined at 1.2A resolution using the MAD method and bromide ions. The structure of ALY-1 is abundant in beta-strands and has a deep cleft, similar to the jellyroll beta-sandwich found in 1,3-1,4-beta-glucanase. The structure suggests that alginate molecules may penetrate into the cleft to interact with the catalytic site of ALY-1. The reported crystal structure of another type of alginate lyase, A1-III, differs from that of ALY-1 in that it consists almost entirely of alpha-helical structure. Nevertheless, the putative catalytic residues in both enzymes are positioned in space in nearly identical arrangements. This finding suggests that both alginate lyases may have evolved through convergent evolution.
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purification and characterization of bifunctional alginate lyase from alteromonas sp strain no 272 and its action on saturated oligomeric substrates
Bioscience Biotechnology and Biochemistry, 2001Co-Authors: Yoshiko Iwamoto, Ryoko Araki, Kenichi Iriyama, Hisataka Fukuda, Shinziro Hayashida, Tsuyoshi MuramatsuAbstract:A marine bacterium (strain No. 272) isolated from sea mud in Omura Bay produced an alginate lyase and was classified as an Alteromonas species. The enzyme was purified from the culture medium of the bacterium by DEAE-Cellulofine, Sephadex G-100 gel chromatography to an electrophoretically homogeneous state in the presence and absence of SDS. The molecular mass of the enzyme was 23 and 33.9 kDa on Sephadex G-100 column chromatography and SDS-polyacrylamide gel electrophoresis, respectively, with an isoelectric point of 3.8. The predominant secondary structure of the enzyme was found to be most likely beta-structure by circular dichroism. The enzyme was most active at pH 7.5-8.0 and stable around pH 5-11. The enzyme was more labile in Tris-HCI buffer (pH 7.0) to heat treatment, than in phosphate buffer (pH 7.0). No of metal ions significantly affected the enzyme activity. The enzyme acted on sodium alginate in an endo-type manner and on two components of alginate, poly-alpha1,4-L-Guluronate and poly-beta1,4-D-mannuronate, as judged by routine ultraviolet assay (235 nm) and circular dichroic spectral changes of the substrates. However, the coexisting poly-alpha1,4-L-Guluronate and poly-beta1,4-D-mannuronate apparently interacted with the enzyme in a competitive manner. Although the enzyme depolymerized alginate in an endo-type, it did not act on trimeric Guluronate and mannuronate, but on the tetramers or more. The kinetic analyses showed that kcat/Km for each oligomer was larger for the Guluronate oligomers than for the mannuronate ones, and that the subsite structure of the enzyme most likely consisted of six binding sites from the intrinsic reaction rate constant (kint) and intrinsic substrate binding constant (Kint).
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purification and characterization of bifunctional alginate lyase from alteromonas sp strain no 272 and its action on saturated oligomeric substrates
Bioscience Biotechnology and Biochemistry, 2001Co-Authors: Yoshiko Iwamoto, Ryoko Araki, Kenichi Iriyama, Hisataka Fukuda, Shinziro Hayashida, Tsuyoshi MuramatsuAbstract:A marine bacterium (strain No. 272) isolated from sea mud in Omura Bay produced an alginate lyase and was classified as an Alteromonas species. The enzyme was purified from the culture medium of the bacterium by DEAE-Cellulofine, Sephadex G-100 gel chromatography to an electrophoretically homogeneous state in the presence and absence of SDS. The molecular mass of the enzyme was 23 and 33.9kDa on Sephadex G-100 column chromatography and SDS-polyacrylamide gel electrophoresis, respectively, with an isoelectric point of 3.8. The predominant secondary structure of the enzyme was found to be most likely β-structure by circular dichroism. The enzyme was most active at pH 7.5-8.0 and stable around pH 5-11. The enzyme was more labile in Tris-HCl buffer (pH 7.0) to heat treatment, than in phosphate buffer (pH 7.0). No of metal ions significantly affected the enzyme activity. The enzyme acted on sodium alginate in an endo-type manner and on two components of alginate, poly-α1,4-L-Guluronate and poly-β1,4-D-mannuron...
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cloning and sequence analysis of a gene aly pg encoding poly α l Guluronate lyase from corynebacterium sp strain aly 1
Journal of Bioscience and Bioengineering, 2000Co-Authors: Yasuhito Matsubara, Tatsuya Oda, Kenichi Iwasaki, Ryoko Kawada, Yoshio Kimura, Tsuyoshi MuramatsuAbstract:The aly PG gene, coding for a poly alpha-l-Guluronate lyase (PG lyase) of Corynebacterium strain ALY-1, was cloned and sequenced. The gene consists of 768 bp encoding a signal peptide of 32 amino acids and a mature protein of 224 amino acids. Two disulfide bond cross-linkages were found to be formed between Cys-4 and Cys-51 and between Cys-200 and Cys-206 in the native PG lyase molecule. The deduced amino acid sequence of the Corynebacterium sp. aly PG gene exhibited 29% homology toward that of the Klebsiella pneumoniae, subsp. aerogenes aly A gene, with two conserved regions (the amino acid sequences from Y-102 to M-110 and from Y-221 to Q-229).
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action of poly α l Guluronate lyase from corynebacterium sp aly 1 strain on saturated oligoGuluronates
Bioscience Biotechnology and Biochemistry, 1998Co-Authors: Yasuhito Matsubara, Kenichi Iwasaki, Tsuyoshi MuramatsuAbstract:A kinetic analysis of degradation of saturated oligoGuluronates by poly(alpha-L-Guluronate)lyase from Corynebacterium sp. ALY-1 strain was done. The saturated oligoGuluronates were prepared by hydrolyzing poly alpha-1,4-L-Guluronate from alginate with HCl, and then by gel filtration on a Bio-Gel P-6 column. The saturated pentaGuluronate or above were rapidly degraded by the enzyme, while tetraGuluronate was slowly degraded. From the dependency of the catalytic rate constant (kcat) on the degree of polymerization of substrates, the enzyme was found to have a subsite size corresponding to hexaGuluronate units. The action pattern of the enzyme on hexaGuluronate suggested that the catalytic site of the enzyme was matched to the linkage between the second and third uronic residue from the non-reducing end, since the substrate was mainly split into a unsaturated tetramer and a saturated dimer from a HPLC analysis.
Kamal H Bouhadir - One of the best experts on this subject based on the ideXlab platform.
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sustained and controlled release of daunomycin from cross linked poly aldehyde Guluronate hydrogels
Journal of Pharmaceutical Sciences, 2000Co-Authors: Kamal H Bouhadir, Kuen Yong Lee, Geneveive M Kruger, David J MooneyAbstract:We have incorporated daunomycin, an antineoplastic agent, into a biodegradable hydrogel through a labile covalent bond. In brief, sodium alginate was chemically broken down to low molecular weight and followed by oxidation to prepare poly(aldehyde Guluronate). Adipic dihydrazide was used to incorporate the drug into the polymer backbone and cross-link the polymer to form hydrogels. Daunomycin can be released from the hydrogel after the hydrolysis of the covalent linkage between the drug and the polymer. A wide range of release profiles of daunomycin (e.g., from 2 days to 6 weeks) has been achieved using these materials, and the biological activity of the released daunomycin was maintained.
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degradation behavior of covalently cross linked poly aldehyde Guluronate hydrogels
Macromolecules, 2000Co-Authors: Kuen Yong Lee, Kamal H Bouhadir, David J MooneyAbstract:There is a significant need in the biomedical field for hydrogels with controllable mechanical and degradative properties. We now report the degradation behavior of novel hydrogels formed by the cr...
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synthesis of cross linked poly aldehyde Guluronate hydrogels
Polymer, 1999Co-Authors: Kamal H Bouhadir, Debra S Hausman, David J MooneyAbstract:Alginate is an attractive material for controlled drug delivery and cell transplantation applications. However, alginate hydrogels are not degradable, have limited mechanical properties, and lack the functional groups required for cell interaction. To address these limitations of alginate while maintaining their favorable characteristics, we have synthesized new polymers derived from sodium poly(Guluronate), the portion of the alginate molecule that is responsible for its gelling behaviour. Sodium poly(Guluronate) was isolated, oxidized with sodium periodate, and cross-linked with adipic dihydrazide to yield hydrogels with a wide range of mechanical properties, and with cell adhesion peptides coupled to their backbones.
Kuen Yong Lee - One of the best experts on this subject based on the ideXlab platform.
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degradable and injectable poly aldehyde Guluronate hydrogels for bone tissue engineering
Journal of Biomedical Materials Research, 2001Co-Authors: Kuen Yong Lee, Eben Alsberg, David J MooneyAbstract:Degradable and injectable hydrogels may be ideal for bone-tissue engineering, especially in the craniofacial region because of the ease of access for injection. Alginate hydrogels potentially could be used as injectable cell delivery vehicles, but they exhibit a limited range of mechanical properties and uncontrollable disintegration time. Therefore we synthesized new hydrogels, composed of poly(aldehyde Guluronate) (PAG) and adipic acid dihydrazide, that have a wide range of mechanical stiffness and controllable degradation rate. MC3T3-E1 cells adhered and multiplied on PAG hydrogels in vitro. When primary rat calvarial osteoblasts were mixed with PAG hydrogels and subcutaneously injected into the backs of mice, mineralized bone tissues were formed 9 weeks following implantation. These hydrogels may find wide utility as an injectable delivery system for bone precursor cells as well as for other applications in tissue engineering.
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sustained and controlled release of daunomycin from cross linked poly aldehyde Guluronate hydrogels
Journal of Pharmaceutical Sciences, 2000Co-Authors: Kamal H Bouhadir, Kuen Yong Lee, Geneveive M Kruger, David J MooneyAbstract:We have incorporated daunomycin, an antineoplastic agent, into a biodegradable hydrogel through a labile covalent bond. In brief, sodium alginate was chemically broken down to low molecular weight and followed by oxidation to prepare poly(aldehyde Guluronate). Adipic dihydrazide was used to incorporate the drug into the polymer backbone and cross-link the polymer to form hydrogels. Daunomycin can be released from the hydrogel after the hydrolysis of the covalent linkage between the drug and the polymer. A wide range of release profiles of daunomycin (e.g., from 2 days to 6 weeks) has been achieved using these materials, and the biological activity of the released daunomycin was maintained.
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degradation behavior of covalently cross linked poly aldehyde Guluronate hydrogels
Macromolecules, 2000Co-Authors: Kuen Yong Lee, Kamal H Bouhadir, David J MooneyAbstract:There is a significant need in the biomedical field for hydrogels with controllable mechanical and degradative properties. We now report the degradation behavior of novel hydrogels formed by the cr...
Wojciech Plazinski - One of the best experts on this subject based on the ideXlab platform.
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binding of bivalent metal cations by α l Guluronate insights from the dft md simulations
New Journal of Chemistry, 2015Co-Authors: Wojciech Plazinski, Mateusz DrachAbstract:The negatively charged polyuronates exhibit a high affinity for binding the bivalent metal cations. This feature is used for the removal of heavy metals from aqueous solutions. The aim of the present paper is to: (i) present the computational strategy, helpful in simulating the metal ion–uronate complexes; (ii) illustrate its applicability to the example of the α-L-Guluronate anion (the monomeric unit of alginates) interacting with bivalent metal ions: Zn2+, Cu2+, Cd2+, Mn2+ and Co2+. The study was carried out on the basis of the ‘hybrid’ molecular dynamics simulations in which the selected part of the system (uronate anions and metal cations) is treated with the ab initio level of accuracy, whereas the interactions within the rest of the system are approximated by the classical force fields. The results allowed for determining the basic structural and energetic (for example, the free energy profiles associated with the cation binding–unbinding process) characteristics related to the metal ion–Guluronate complexes. Most of the studied ions exhibited the preference for monodentate binding. Bidentate binding can be observed for Mn2+ and Co2+ (dominant binding mode) and Cd2+ (secondary binding mode). The calculated binding free energy order (Cu > Co > Zn ∼ Mn > Cd) follows both the experimentally determined order of transition metal ion–alginate affinities and the metal–uronate interaction energies. The efficiency of the calculations and the general characteristics of the method allow for its potential use in simulations of other uronate–metal ion systems, increasing the range of methods which can be used for studying the metal biosorption processes.
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calcium α l Guluronate complexes ca2 binding modes from dft md simulations
Journal of Physical Chemistry B, 2013Co-Authors: Wojciech Plazinski, Mateusz DrachAbstract:The interactions of divalent calcium ions with a single α-L-Guluronate anion and oligo(α-L-Guluronate) chain have been studied in terms of the 'hybrid' molecular dynamics technique in which the selected parts of the system are treated with different level of theory (DFT-MD). The simulations were focused on obtaining the free energy profiles designed to clarify the possible calcium binding modes. In all considered cases, the calcium ion is coordinated by carboxyl oxygen atoms and water molecules exclusively. The results allowed for (i) determining the dentacy of calcium binding; (ii) estimating the calcium binding/unbinding-related free energy profiles; and (iii) positive verification of the previously [J. Comput. Chem. 2011, 32, 2988] proposed modification of the egg-box model describing the calcium alginate/Guluronate structure. Additionally, the findings indicate that the polarization of the carboxyl group induced by the presence of Ca(2+) ion causes the increase of the free energy barrier separating the 'free' and 'bound' states of Ca(2+), in comparison to the classical biomolecular force fields (GROMOS/SPC and GLYCAM/TIP3P).
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thermodynamic aspects of calcium binding by poly α l Guluronate chains a molecular simulation study
Applied Surface Science, 2012Co-Authors: Wojciech Plazinski, Mateusz DrachAbstract:Abstract The theoretical studies on binding of calcium ions by poly(α- l -Guluronate) chains were carried out to provide the insight into the molecular basis of this process. The three local minima of the Gibbs free energy (corresponding to the two distinct stable states and to the one short living, meta-stable state) were distinguished. The results emphasize the important role of water molecules. The ECN (effective coordination number) parameter was introduced in order to describe the dynamic changes in the arrangement of solvent molecules coordinating calcium ion.
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molecular modeling of ca2 oligo α l Guluronate complexes toward the understanding of the junction zone structure in calcium alginate gels
Structural Chemistry, 2012Co-Authors: Wojciech Plazinski, Wladyslaw RudzinskiAbstract:Gelling of alginates in the presence of divalent metal ions is accompanied by the formation of the junction zone, i.e., the region of the alginate chains aggregation. The structure of the junction zone results primarily from the nature of interaction between the “dimers,” created by two alginate chains connected via Ca2+ ions. We have applied the molecular dynamics technique, in combination with the GROMOS96 biomolecular force field to elucidate the structural features and the stability of such dimer–dimer complexes, where the alginate chains were represented by oligomers of α-l-Guluronate. The results indicate that only associations mediated by calcium ions and carboxylic groups are stable during simulations. Hydrogen bonding-type interactions are too weak to support the stability of complexes. The parallel arrangement of two dimers is the favorable one, due to their helical twists, which interfere with the formation of the fully ordered structure of the junction zone.
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molecular basis of calcium binding by polyGuluronate chains revising the egg box model
Journal of Computational Chemistry, 2011Co-Authors: Wojciech PlazinskiAbstract:The egg-box model is the commonly accepted description of the calcium alginate/Guluronate structure. It assumes that calcium ions are bound in the periodic chelation sites located between two polyuronate chains. This study was focused on elucidating the nature of interactions between calcium and polyuronates, responsible for the Ca2+-induced association of polyuronate chains in the aqueous solutions. Both molecular dynamics and semiempirical (ZINDO-1/Monte Carlo) methods were used for this purpose. Based on the obtained results, new structural models of Ca2+-polyGuluronate complexes were proposed both for parallel and antiparallel pairing. Contrary to the classical egg-box model, Ca2+ ions are coordinated by four carboxyl oxygens from two opposite carboxyl groups belonging to two different polyGuluronate chains and, additionally, by four oxygen atoms belonging to water molecules. Such a coordination pattern can be interpreted as the result of competition between water molecules and carboxylic groups of polyGuluronate for calcium ions. Other structural details (the network of hydrogen bonds, for instance) are close to those corresponding to the “shifted” egg-box model proposed by Braccini and Perez (Biomacromolecules 2001, 2, 1089) and remain in agreement with the experimental data. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011