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Harry R. Allcock - One of the best experts on this subject based on the ideXlab platform.
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miscibility of choline substituted polyphosphazenes with plga and osteoblast activity on resulting blends
Biomaterials, 2010Co-Authors: Arlin L. Weikel, Lakshmi S. Nair, Cato T. Laurencin, Steven G Owens, Nicole L Morozowich, Meng Deng, Harry R. AllcockAbstract:The preparation of phosphazene tissue engineering scaffolds with bioactive side groups has been accomplished using the biological buffer, choline chloride. Mixed-substituent phosphazene cyclic trimers (as model systems) and polymers with choline chloride and Glycine Ethyl Ester, alanine Ethyl Ester, valine Ethyl Ester, or phenylalanine Ethyl Ester were synthesized. Two different synthetic protocols were examined. A sodium hydride mediated route resulted in polyphosphazenes with a low choline content, while a cesium carbonate mediated process produced polyphosphazenes with higher choline content. The phosphazene structures and physical properties were studied using multinuclear NMR, differential scanning calorimetry (DSC), and gel permeation chromatography (GPC) techniques. The resultant polymers were then blended with PLGA (50:50) or PLGA (85:15) and characterized by DSC analysis and scanning electron microscopy (SEM). Polymer products obtained via the sodium hydride route produced miscible blends with both ratios of PLGA, while the cesium carbonate route yielded products with reduced blend miscibility. Heterophase hydrolysis experiments in aqueous media revealed that the polymer blends hydrolyzed to near-neutral pH media (∼5.8 to 6.8). The effect of different molecular structures on cellular adhesion showed osteoblast proliferation with an elevated osteoblast phenotype expression compared to PLGA over a 21-day culture period.
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hydrogen bonding in blends of polyEsters with dipeptide containing polyphosphazenes
Journal of Applied Polymer Science, 2010Co-Authors: Nick R. Krogman, Lakshmi S. Nair, Cato T. Laurencin, Arlin L. Weikel, Katherine A. Kristhart, Syam P. Nukavarapu, Nhu Q Nguyen, Harry R. AllcockAbstract:New biomedically erodible polymer composites were investigated. Polyphosphazenes containing the dipeptide side groups alanyl–Glycine Ethyl Ester, valinyl–Glycine Ethyl Ester, and phenylalanyl–Glycine Ethyl Ester were blended with poly(lactide-co-glycolide) (PLGA) with lactic to glycolic acid ratios of 50 : 50 [PLGA (50 : 50)] and 85 : 15 [PLGA (85 : 15)] with solution-phase techniques. Each dipeptide Ethyl Ester side group contains two NH protons that are capable of hydrogen bonding with the carbonyl functions of PLGA. Polyphosphazenes that contain only the dipeptide Ethyl Ester groups are insoluble in organic solvents and are thus unsuitable for solution-phase composite formation. To ensure solubility during and after synthesis, cosubstituted polymers with both dipeptide Ethyl Ester and Glycine or alanine Ethyl Ester side groups were used. Solution casting or electrospinning was used to fabricate polymer blend matrices with different ratios of polyphosphazene to polyEster, and their miscibilities were estimated with differential scanning calorimetry and scanning electron microscopy techniques. Polyphosphazenes with alanyl–Glycine Ethyl Ester side groups plus the second cosubstituent were completely miscible with PLGA (50 : 50) and PLGA (85 : 15) when processed via solution-casting techniques. This suggests that the hydrogen-bonding protons in alanyl–Glycine Ethyl Ester have access to the oxygen atoms of the carbonyl units in PLGA. However, when the same pair of polymers was electrospun from solution, the polymers proved to be immiscible. Solution-cast miscible polymer blends were obtained from PLGA (50 : 50) plus the polyphosphazene that was cosubstituted with valinyl–Glycine Ethyl Ester and Glycine Ethyl Ester side groups. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
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polyphosphazenes that contain dipeptide side groups synthesis characterization and sensitivity to hydrolysis
Macromolecules, 2009Co-Authors: Arlin L. Weikel, Lakshmi S. Nair, Nick R. Krogman, Cato T. Laurencin, Nhu Q Nguyen, Harry R. AllcockAbstract:The dipeptides alanyl-Glycine Ethyl Ester, valinyl-Glycine Ethyl Ester, and phenylalanyl-Glycine Ethyl Ester were synthesized by mixed anhydride solution-phase peptide reactions. The free N-terminus was used as a reactive site for nucleophilic replacement of the chlorine atoms in poly(dichlorophosphazene). The C-terminus was protected with an Ethyl Ester to prevent side reactions and cross-linking. The alanyl-Glycine Ethyl Ester replaced all the chlorine atoms in poly(dichlorophosphazene). However, replacement of all the chlorine atoms in poly(dichlorophosphazene) by valinyl-Glycine Ethyl Ester or phenylalanyl-Glycine Ethyl Ester polyphosphazenes was prevented by the insolubility of the partially substituted intermediates. To circumvent this problem, cosubstitution was carried out using the valinyl- or phenylalanyl Esters with Glycine Ethyl Ester or alanine Ethyl Ester in a 1:1 ratio. Cosubstituted polyphosphazenes with alanyl Glycine Ethyl Ester and Glycine Ethyl Ester or alanine Ethyl Ester were also sy...
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synthesis of purine and pyrimidine containing polyphosphazenes physical properties and hydrolytic behavior
Macromolecules, 2008Co-Authors: Nick R. Krogman, Lakshmi S. Nair, Cato T. Laurencin, Mark D Hindenlang, Harry R. AllcockAbstract:We report here the first examples of poly(organophosphazenes) with side groups derived from the purines guanine and adenine and the pyrimidine cytosine. Polymers with these purines or pyrimidines as the only side groups proved difficult to synthesize by macromolecular substitution techniques because of the insolubility of the intermediate products. Therefore, cosubstitution reactions of the poly(dichlorophosphazene) with Glycine Ethyl Ester, alanine Ethyl Ester, or diEthylene glycol mEthyl ether, followed by the respective purine or pyrimidine, were utilized. Each pair of side groups was incorporated into the polyphosphazene in a 1:1 ratio. 31P NMR spectroscopy verified the replacement of all the chlorine atoms, while 1H and 13C NMR techniques confirmed the presence and ratio of the different side group. DRIFT spectroscopy indicated that the attachment of the purines or pyrimidines was via the primary amino functionality. Glass transition temperatures ranged from −28 to −15 °C for the mixed-substituent po...
Michael L. Gross - One of the best experts on this subject based on the ideXlab platform.
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isotope encoded carboxyl group footprinting for mass spectrometry based protein conformational studies
Journal of the American Society for Mass Spectrometry, 2016Co-Authors: Hao Zhang, Michael L. GrossAbstract:We report an isotope-encoding method coupled with carboxyl-group footprinting to monitor protein conformational changes. The carboxyl groups of aspartic/glutamic acids and of the C-terminus of proteins can serve as reporters for protein conformational changes when labeled with Glycine Ethyl Ester (GEE) mediated by carbodiimide. In the new development, isotope-encoded “heavy” and “light” GEE are used to label separately the two states of the orange carotenoid protein (OCP) from cyanobacteria. Two samples are mixed (1:1 ratio) and analyzed by a single LC-MS/MS experiment. The differences in labeling extent between the two states are represented by the ratio of the “heavy” and “light” peptides, providing information about protein conformational changes. Combining isotope-encoded MS quantitative analysis and carboxyl-group footprinting reduces the time of MS analysis and improves the sensitivity of GEE and other footprinting.
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mass spectrometry based protein footprinting characterizes the structures of oligomeric apolipoprotein e2 e3 and e4
Biochemistry, 2011Co-Authors: Brian Gau, Kanchan Garai, Carl Frieden, Michael L. GrossAbstract:The three common isoforms of apolipoprotein E (ApoE) differ at two sites in their 299 amino acid sequence; these differences modulate the structure of ApoE to affect profoundly the isoform associations with disease. The e4 allele in particular is strongly associated with Alzheimer’s disease. The study of the structural effects of these mutation sites in aqueous media is hampered by the aggregation proclivity of each ApoE isoform. Hence, understanding the differences between isoforms has thus far relied on lower resolution biophysical measurements, mutagenesis, homology studies, and the use of truncated ApoE variants. In this study, we report two comparative studies of the ApoE family by using the mass spectrometry-based protein footprinting methods of FPOP and Glycine Ethyl Ester (GEE) labeling. The first experiment examines the three full-length WT isoforms in their tetrameric state and finds that the overall structures are similar, with the exception of M108 in ApoE4 which is more solvent-accessible in ...
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carboxyl group footprinting maps the dimerization interface and phosphorylation induced conformational changes of a membrane associated tyrosine kinase
Molecular & Cellular Proteomics, 2011Co-Authors: Hao Zhang, Don L Rempel, John Monsey, Ilan Vidavsky, Michael L. Gross, Wei Shen, Ron BoseAbstract:: Her4 is a transmembrane receptor tyrosine kinase belonging to the ErbB-EGFR family. It plays a vital role in the cardiovascular and nervous systems, and mutations in Her4 have been found in melanoma and lung cancer. The kinase domain of Her4 forms a dimer complex, called the asymmetric dimer, which results in kinase activation. Although a crystal structure of the Her4 asymmetric dimer is known, the dimer affinity and the effect of the subsequent phosphorylation steps on kinase domain conformation are unknown. We report here the use of carboxyl-group footprinting MS on a recombinant expressed, Her4 kinase-domain construct to address these questions. Carboxyl-group footprinting uses a water-soluble carbodiimide, 1-Ethyl-3-(3-dimEthylaminopropyl)carbodiimide, in the presence of Glycine Ethyl Ester, to modify accessible carboxyl groups on glutamate and aspartate residues. Comparisons of Her4 kinase-domain monomers versus dimers and of unphosphorylated versus phosphorylated dimers were made to map the dimerization interface and to determine phosphorylation induced-conformational changes. We detected 37 glutamate and aspartate residues that were modified, and we quantified their extents of modification by liquid chromatography MS. Five residues showed changes in carboxyl-group modification. Three of these residues are at the predicted dimer interface, as shown by the crystal structure, and the remaining two residues are on loops that likely have altered conformation in the kinase dimer. Incubating the Her4 kinase dimers with ATP resulted in dramatic increase in Tyr-850 phosphorylation, located on the activation loop, and this resulted in a conformational change in this loop, as evidenced by reduction in carboxyl-group modification. The kinase monomer-dimer equilibrium was measured using a titration format in which the extent of carboxyl-group footprinting was mathematically modeled to give the dimer association constant (1.5-6.8 × 10(12) dm(2)/mol). This suggests that the kinase-domain makes a significant contribution to the overall dimerization affinity of the full-length Her4 protein.
Peter T.m. Kenny - One of the best experts on this subject based on the ideXlab platform.
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the electron transport mechanism in Ester and its influence on bioactivity in the anticancer drug n 6 ferrocenyl 2 naphthoyl l alanine Glycine Ethyl Ester fnlagee
AIP Conference Proceedings, 2018Co-Authors: Geethu Sudhi, Peter T.m. Kenny, T S Xavier, S R Rajina, S G Praveen, J BinoyAbstract:The reactivity of Ester group plays key role in inducing bioactivity of many ferrocenyl biconjugated compounds. The Ester reactivity can be explained, based on electron transport mechanism using vibrational spectroscopy, aided by DFT simulation. The FT IR and FT Raman spectral measurements have been carried out for N-(6-ferrocenyl-2-naphthoyl)-L-alanine-Glycine Ethyl Ester (FNLAGEE) and the optimized geometry and vibrational spectra have been computed using DFT method, at B3LYP/LANL2DZ level of theory. The cis conformation of Ester and electron transport mechanism, thus analyzed, has been correlated to the geometry and the spectral characteristics of Ester. To investigate the bioactivity and binding interactions of the molecule, molecular docking simulations and UV-Vis absorption studies of FNLAGEE with BSA and DNA has been performed.
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ft ir and raman spectroscopic and dft studies of anti cancer active molecule n meta ferrocenyl benzoyl l alanine Glycine Ethyl Ester
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2015Co-Authors: T S Xavier, Peter T.m. Kenny, D Manimaran, Hubert I JoeAbstract:FT-Raman and FT-IR spectra of N-{(meta-ferrocenyl) Benzoyl} - l-alanine - Glycine Ethyl Ester were recorded in solid phase. The optimized molecular geometry, the vibrational wavenumbers, the infrared intensities and the Raman scattering intensities were calculated by using density functional method(B3LYP) with 6-31G(d, p) basis set. Vibrational assignment of the molecule was done by using potential energy distribution analysis. Natural bond orbital analysis, Mulliken charge analysis and HOMO-LUMO energy were used to elucidate the reasons for intra molecular charge transfer. Docking studies were conducted to predict its anticancer activity.
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n ortho ferrocenyl benzoyl dipeptide Esters synthesis structural characterization and in vitro anti cancer activity of n ortho ferrocenyl benzoyl Glycine l alanine Ethyl Ester and n ortho ferrocenyl benzoyl l alanine Glycine Ethyl Ester
Journal of Organometallic Chemistry, 2007Co-Authors: Alan J Corry, Steven Alley, Paula N Kelly, Dermot Osullivan, Alok Goel, David Savage, Peter T.m. KennyAbstract:Abstract N-ortho-ferrocenyl benzoyl dipeptide Esters 2–6 were prepared by coupling ortho-ferrocenyl benzoic acid 1 to the dipeptide Ethyl Esters GlyGly(OEt) (2), GlyAla(OEt) (3), GlyPhe(OEt) (4), AlaGly(OEt) (5) and AlaPhe(OEt) (6). The compounds were fully characterized by a range of NMR spectroscopic techniques, mass spectrometry and cyclic voltammetry. The cytotoxicity of 3 and 5 towards lung cancer cells has been determined.
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the synthesis and structural characterization of novel n meta ferrocenyl benzoyl dipeptide Esters the x ray crystal structure and in vitro anti cancer activity of n meta ferrocenyl benzoyl l alanine Glycine Ethyl Ester
Journal of Organometallic Chemistry, 2007Co-Authors: Alok Goel, Steven Alley, Paula N Kelly, Dermot Osullivan, Helge Muellerbunz, David Savage, Peter T.m. KennyAbstract:Abstract A series of N - meta -ferrocenyl benzoyl dipeptide Esters 2 – 5 have been prepared by coupling meta -ferrocenyl benzoic acid 1b to the dipeptide Ethyl Esters using the conventional 1,3-dicyclohexylcarbodiimide (DCC), 1-hydroxybenzotriazole (HOBt) protocol. The dipeptides employed in the synthesis were AlaGly(OEt) ( 2 ), AlaAla(OEt) ( 3 ), AlaLeu(OEt) ( 4 ) and AlaPhe(OEt) ( 5 ). The compounds were fully characterized by a range of NMR spectroscopic techniques, mass spectrometry (MALDI-MS, ESI-MS), and cyclic voltammetry (CV). In addition, the X-ray crystal structure and cytotoxicity of N -{ meta -(ferrocenyl)-benzoyl}- l -alanine-Glycine Ethyl Ester ( 2 ) towards lung cancer cells has been determined.
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the synthesis and structural characterization of n para ferrocenyl benzoyl dipeptide Esters the x ray crystal structure of n para ferrocenyl benzoyl l alanine Glycine Ethyl Ester
Journal of Organometallic Chemistry, 2006Co-Authors: Alok Goel, Steven Alley, Paula N Kelly, David Savage, Tara Hogan, Sylvia M Draper, Christopher M Fitchett, Peter T.m. KennyAbstract:A series of N - para -ferrocenyl benzoyl dipeptide Esters 2 – 5 were prepared by coupling para -ferrocenyl benzoic acid ( 1 ) to the dipeptide Ethyl Esters using the conventional 1,3-dicyclohexylcarbodiimide (DCC), 1-hydroxybenzotriazole (HOBt) protocol. The dipeptides employed in the synthesis were Ala-Gly(OEt) ( 2 ), Ala-Ala(OEt) ( 3 ), Ala-Leu(OEt) ( 4 ) and Ala-Phe(OEt) ( 5 ). The compounds were fully characterized by a range of NMR spectroscopic techniques, electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS). In addition the X-ray crystal structure of the l -alanine-Glycine derivative 2 has been determined.
Lakshmi S. Nair - One of the best experts on this subject based on the ideXlab platform.
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miscibility of choline substituted polyphosphazenes with plga and osteoblast activity on resulting blends
Biomaterials, 2010Co-Authors: Arlin L. Weikel, Lakshmi S. Nair, Cato T. Laurencin, Steven G Owens, Nicole L Morozowich, Meng Deng, Harry R. AllcockAbstract:The preparation of phosphazene tissue engineering scaffolds with bioactive side groups has been accomplished using the biological buffer, choline chloride. Mixed-substituent phosphazene cyclic trimers (as model systems) and polymers with choline chloride and Glycine Ethyl Ester, alanine Ethyl Ester, valine Ethyl Ester, or phenylalanine Ethyl Ester were synthesized. Two different synthetic protocols were examined. A sodium hydride mediated route resulted in polyphosphazenes with a low choline content, while a cesium carbonate mediated process produced polyphosphazenes with higher choline content. The phosphazene structures and physical properties were studied using multinuclear NMR, differential scanning calorimetry (DSC), and gel permeation chromatography (GPC) techniques. The resultant polymers were then blended with PLGA (50:50) or PLGA (85:15) and characterized by DSC analysis and scanning electron microscopy (SEM). Polymer products obtained via the sodium hydride route produced miscible blends with both ratios of PLGA, while the cesium carbonate route yielded products with reduced blend miscibility. Heterophase hydrolysis experiments in aqueous media revealed that the polymer blends hydrolyzed to near-neutral pH media (∼5.8 to 6.8). The effect of different molecular structures on cellular adhesion showed osteoblast proliferation with an elevated osteoblast phenotype expression compared to PLGA over a 21-day culture period.
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hydrogen bonding in blends of polyEsters with dipeptide containing polyphosphazenes
Journal of Applied Polymer Science, 2010Co-Authors: Nick R. Krogman, Lakshmi S. Nair, Cato T. Laurencin, Arlin L. Weikel, Katherine A. Kristhart, Syam P. Nukavarapu, Nhu Q Nguyen, Harry R. AllcockAbstract:New biomedically erodible polymer composites were investigated. Polyphosphazenes containing the dipeptide side groups alanyl–Glycine Ethyl Ester, valinyl–Glycine Ethyl Ester, and phenylalanyl–Glycine Ethyl Ester were blended with poly(lactide-co-glycolide) (PLGA) with lactic to glycolic acid ratios of 50 : 50 [PLGA (50 : 50)] and 85 : 15 [PLGA (85 : 15)] with solution-phase techniques. Each dipeptide Ethyl Ester side group contains two NH protons that are capable of hydrogen bonding with the carbonyl functions of PLGA. Polyphosphazenes that contain only the dipeptide Ethyl Ester groups are insoluble in organic solvents and are thus unsuitable for solution-phase composite formation. To ensure solubility during and after synthesis, cosubstituted polymers with both dipeptide Ethyl Ester and Glycine or alanine Ethyl Ester side groups were used. Solution casting or electrospinning was used to fabricate polymer blend matrices with different ratios of polyphosphazene to polyEster, and their miscibilities were estimated with differential scanning calorimetry and scanning electron microscopy techniques. Polyphosphazenes with alanyl–Glycine Ethyl Ester side groups plus the second cosubstituent were completely miscible with PLGA (50 : 50) and PLGA (85 : 15) when processed via solution-casting techniques. This suggests that the hydrogen-bonding protons in alanyl–Glycine Ethyl Ester have access to the oxygen atoms of the carbonyl units in PLGA. However, when the same pair of polymers was electrospun from solution, the polymers proved to be immiscible. Solution-cast miscible polymer blends were obtained from PLGA (50 : 50) plus the polyphosphazene that was cosubstituted with valinyl–Glycine Ethyl Ester and Glycine Ethyl Ester side groups. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
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polyphosphazenes that contain dipeptide side groups synthesis characterization and sensitivity to hydrolysis
Macromolecules, 2009Co-Authors: Arlin L. Weikel, Lakshmi S. Nair, Nick R. Krogman, Cato T. Laurencin, Nhu Q Nguyen, Harry R. AllcockAbstract:The dipeptides alanyl-Glycine Ethyl Ester, valinyl-Glycine Ethyl Ester, and phenylalanyl-Glycine Ethyl Ester were synthesized by mixed anhydride solution-phase peptide reactions. The free N-terminus was used as a reactive site for nucleophilic replacement of the chlorine atoms in poly(dichlorophosphazene). The C-terminus was protected with an Ethyl Ester to prevent side reactions and cross-linking. The alanyl-Glycine Ethyl Ester replaced all the chlorine atoms in poly(dichlorophosphazene). However, replacement of all the chlorine atoms in poly(dichlorophosphazene) by valinyl-Glycine Ethyl Ester or phenylalanyl-Glycine Ethyl Ester polyphosphazenes was prevented by the insolubility of the partially substituted intermediates. To circumvent this problem, cosubstitution was carried out using the valinyl- or phenylalanyl Esters with Glycine Ethyl Ester or alanine Ethyl Ester in a 1:1 ratio. Cosubstituted polyphosphazenes with alanyl Glycine Ethyl Ester and Glycine Ethyl Ester or alanine Ethyl Ester were also sy...
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synthesis of purine and pyrimidine containing polyphosphazenes physical properties and hydrolytic behavior
Macromolecules, 2008Co-Authors: Nick R. Krogman, Lakshmi S. Nair, Cato T. Laurencin, Mark D Hindenlang, Harry R. AllcockAbstract:We report here the first examples of poly(organophosphazenes) with side groups derived from the purines guanine and adenine and the pyrimidine cytosine. Polymers with these purines or pyrimidines as the only side groups proved difficult to synthesize by macromolecular substitution techniques because of the insolubility of the intermediate products. Therefore, cosubstitution reactions of the poly(dichlorophosphazene) with Glycine Ethyl Ester, alanine Ethyl Ester, or diEthylene glycol mEthyl ether, followed by the respective purine or pyrimidine, were utilized. Each pair of side groups was incorporated into the polyphosphazene in a 1:1 ratio. 31P NMR spectroscopy verified the replacement of all the chlorine atoms, while 1H and 13C NMR techniques confirmed the presence and ratio of the different side group. DRIFT spectroscopy indicated that the attachment of the purines or pyrimidines was via the primary amino functionality. Glass transition temperatures ranged from −28 to −15 °C for the mixed-substituent po...
Cato T. Laurencin - One of the best experts on this subject based on the ideXlab platform.
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miscibility of choline substituted polyphosphazenes with plga and osteoblast activity on resulting blends
Biomaterials, 2010Co-Authors: Arlin L. Weikel, Lakshmi S. Nair, Cato T. Laurencin, Steven G Owens, Nicole L Morozowich, Meng Deng, Harry R. AllcockAbstract:The preparation of phosphazene tissue engineering scaffolds with bioactive side groups has been accomplished using the biological buffer, choline chloride. Mixed-substituent phosphazene cyclic trimers (as model systems) and polymers with choline chloride and Glycine Ethyl Ester, alanine Ethyl Ester, valine Ethyl Ester, or phenylalanine Ethyl Ester were synthesized. Two different synthetic protocols were examined. A sodium hydride mediated route resulted in polyphosphazenes with a low choline content, while a cesium carbonate mediated process produced polyphosphazenes with higher choline content. The phosphazene structures and physical properties were studied using multinuclear NMR, differential scanning calorimetry (DSC), and gel permeation chromatography (GPC) techniques. The resultant polymers were then blended with PLGA (50:50) or PLGA (85:15) and characterized by DSC analysis and scanning electron microscopy (SEM). Polymer products obtained via the sodium hydride route produced miscible blends with both ratios of PLGA, while the cesium carbonate route yielded products with reduced blend miscibility. Heterophase hydrolysis experiments in aqueous media revealed that the polymer blends hydrolyzed to near-neutral pH media (∼5.8 to 6.8). The effect of different molecular structures on cellular adhesion showed osteoblast proliferation with an elevated osteoblast phenotype expression compared to PLGA over a 21-day culture period.
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hydrogen bonding in blends of polyEsters with dipeptide containing polyphosphazenes
Journal of Applied Polymer Science, 2010Co-Authors: Nick R. Krogman, Lakshmi S. Nair, Cato T. Laurencin, Arlin L. Weikel, Katherine A. Kristhart, Syam P. Nukavarapu, Nhu Q Nguyen, Harry R. AllcockAbstract:New biomedically erodible polymer composites were investigated. Polyphosphazenes containing the dipeptide side groups alanyl–Glycine Ethyl Ester, valinyl–Glycine Ethyl Ester, and phenylalanyl–Glycine Ethyl Ester were blended with poly(lactide-co-glycolide) (PLGA) with lactic to glycolic acid ratios of 50 : 50 [PLGA (50 : 50)] and 85 : 15 [PLGA (85 : 15)] with solution-phase techniques. Each dipeptide Ethyl Ester side group contains two NH protons that are capable of hydrogen bonding with the carbonyl functions of PLGA. Polyphosphazenes that contain only the dipeptide Ethyl Ester groups are insoluble in organic solvents and are thus unsuitable for solution-phase composite formation. To ensure solubility during and after synthesis, cosubstituted polymers with both dipeptide Ethyl Ester and Glycine or alanine Ethyl Ester side groups were used. Solution casting or electrospinning was used to fabricate polymer blend matrices with different ratios of polyphosphazene to polyEster, and their miscibilities were estimated with differential scanning calorimetry and scanning electron microscopy techniques. Polyphosphazenes with alanyl–Glycine Ethyl Ester side groups plus the second cosubstituent were completely miscible with PLGA (50 : 50) and PLGA (85 : 15) when processed via solution-casting techniques. This suggests that the hydrogen-bonding protons in alanyl–Glycine Ethyl Ester have access to the oxygen atoms of the carbonyl units in PLGA. However, when the same pair of polymers was electrospun from solution, the polymers proved to be immiscible. Solution-cast miscible polymer blends were obtained from PLGA (50 : 50) plus the polyphosphazene that was cosubstituted with valinyl–Glycine Ethyl Ester and Glycine Ethyl Ester side groups. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
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polyphosphazenes that contain dipeptide side groups synthesis characterization and sensitivity to hydrolysis
Macromolecules, 2009Co-Authors: Arlin L. Weikel, Lakshmi S. Nair, Nick R. Krogman, Cato T. Laurencin, Nhu Q Nguyen, Harry R. AllcockAbstract:The dipeptides alanyl-Glycine Ethyl Ester, valinyl-Glycine Ethyl Ester, and phenylalanyl-Glycine Ethyl Ester were synthesized by mixed anhydride solution-phase peptide reactions. The free N-terminus was used as a reactive site for nucleophilic replacement of the chlorine atoms in poly(dichlorophosphazene). The C-terminus was protected with an Ethyl Ester to prevent side reactions and cross-linking. The alanyl-Glycine Ethyl Ester replaced all the chlorine atoms in poly(dichlorophosphazene). However, replacement of all the chlorine atoms in poly(dichlorophosphazene) by valinyl-Glycine Ethyl Ester or phenylalanyl-Glycine Ethyl Ester polyphosphazenes was prevented by the insolubility of the partially substituted intermediates. To circumvent this problem, cosubstitution was carried out using the valinyl- or phenylalanyl Esters with Glycine Ethyl Ester or alanine Ethyl Ester in a 1:1 ratio. Cosubstituted polyphosphazenes with alanyl Glycine Ethyl Ester and Glycine Ethyl Ester or alanine Ethyl Ester were also sy...
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synthesis of purine and pyrimidine containing polyphosphazenes physical properties and hydrolytic behavior
Macromolecules, 2008Co-Authors: Nick R. Krogman, Lakshmi S. Nair, Cato T. Laurencin, Mark D Hindenlang, Harry R. AllcockAbstract:We report here the first examples of poly(organophosphazenes) with side groups derived from the purines guanine and adenine and the pyrimidine cytosine. Polymers with these purines or pyrimidines as the only side groups proved difficult to synthesize by macromolecular substitution techniques because of the insolubility of the intermediate products. Therefore, cosubstitution reactions of the poly(dichlorophosphazene) with Glycine Ethyl Ester, alanine Ethyl Ester, or diEthylene glycol mEthyl ether, followed by the respective purine or pyrimidine, were utilized. Each pair of side groups was incorporated into the polyphosphazene in a 1:1 ratio. 31P NMR spectroscopy verified the replacement of all the chlorine atoms, while 1H and 13C NMR techniques confirmed the presence and ratio of the different side group. DRIFT spectroscopy indicated that the attachment of the purines or pyrimidines was via the primary amino functionality. Glass transition temperatures ranged from −28 to −15 °C for the mixed-substituent po...