Mary Cloninger - Academia.edu (original) (raw)
Papers by Mary Cloninger
Organic and Biomolecular Chemistry, 2004
Mannose-TEMPO functionalized G4-PAMAM dendrimers with increasing mannose loadings have been synth... more Mannose-TEMPO functionalized G4-PAMAM dendrimers with increasing mannose loadings have been synthesized and characterized by MALDI-TOF MS and EPR spectroscopy. Analysis of linebroadening effects in the EPR spectra of these dendrimers allowed us to determine the relative presentation of mannose and TEMPO on the dendrimer surface. Hemagglutination assays and affinity chromatography/EPR experiments to assess the activity of the mannose-TEMPO dendrimers with Concanavalin A are presented.
Journal of Physical Chemistry B, Oct 20, 2005
Macromolecules, Mar 29, 2007
... J. Singel, and Mary J. Cloninger*. Department of Chemistry and Biochemistry and Center for Bi... more ... J. Singel, and Mary J. Cloninger*. Department of Chemistry and Biochemistry and Center for Bioinspired Nanomaterials, Montana State University, 108 Gaines Hall, Bozeman, Montana 59717. ... f) Bosman, AW; Jannsen, RAJ; Meijer, EW Macromolecules1997, 30, 3606−3611. ...
Molecular Pharmaceutics, Oct 4, 2016
The development of pathogenic bacteria resistant to current treatments is a major issue facing th... more The development of pathogenic bacteria resistant to current treatments is a major issue facing the world today. Here, the synthesis and biological activity of fourth generation poly(amidoamine) dendrimers decorated with 1-hexadecyl-azoniabicylo[2.2.2]octane (C 16-DABCO), a quaternary ammonium compound known to have antibacterial activity, are described. This highly cationic dendrimer antibiotic was tested against several Gram positive and Gram negative strains of pathogenic bacteria and exhibited activity against both. Higher activity toward the Gram positive strains that were tested was observed. After the antimicrobial activity was assessed, E. coli and B. cereus were subjected to a resistance selection study. This study demonstrated that a multivalent approach to antimicrobial design significantly reduces the likelihood of developing bacterial resistance. Highly cationic dendrimers were also used as pretreatment of a membrane in order to prevent biofilm formation.
International Journal of Molecular Sciences, 2016
Current opinion in drug discovery & development, 2002
Significant timely advances have been made in the synthesis of heterogeneously functionalized den... more Significant timely advances have been made in the synthesis of heterogeneously functionalized dendrimers. Convergent, divergent and other functionalization techniques have been used to create a variety of complex dendrimer motifs with more than one type of surface group. Synthetic advances, as well as pertinent applications of heterogeneously functionalized dendrimers, are reviewed.
ChemBioChem, 2014
By using lactose-functionalized poly(amidoamine) dendrimers as a tunable multivalent platform, we... more By using lactose-functionalized poly(amidoamine) dendrimers as a tunable multivalent platform, we studied cancer cell aggregation in three different cell lines (A549, DU-145, and HT-1080) with galectin-3. We found that small lactose-functionalized G(2)-dendrimer 1 inhibited galectin-3induced aggregation of the cancer cells. In contrast, dendrimer 4 (a larger, generation 6 dendrimer with 100 carbohydrate end groups) caused cancer cells to aggregate through a galectin-3 pathway. This study indicates that inhibition of cellular aggregation occurred because 1 provided competitive binding sites for galectin-3 (compared to its putative cancer cell ligand, TF-antigen on MUC1). Dendrimer 4, in contrast, provided an excess of ligands for galectin-3 binding; this caused crosslinking and aggregation of cells to be increased.
The Journal of Physical Chemistry B, 2011
The Journal of Physical Chemistry B, 2005
Starburst dendrimers are receiving considerable attention as templates for the assembly of struct... more Starburst dendrimers are receiving considerable attention as templates for the assembly of structured arrays of molecular components. This research motivates the development of improved methods for dendrimer characterizationsspecifically, for determining the numbers, distributions of numbers, and spatial distribution of molecular species synthetically attached to macromolecular templates. Such information provides the basis for advancing strategies aimed at controlling dendrimer functionalization, and thus represents enabling technology for tailoring the composition and structure of molecular arrays fashioned on dendrimer templates. Moreover, this information is vital to the proper interpretation of ongoing experiments in which dendrimers sparsely functionalized with reporter groups are used as probes. In this article, we report MALDI-TOF mass spectrometry and EPR spectroscopy of heterogeneously functionalized G(4)-PAMAM dendrimers bearing nitroxide spin-labels.
Organic & Biomolecular Chemistry, 2005
Manalpha1-2Man functionalized G(3) and G(4)-PAMAM dendrimers have been synthesized and characteri... more Manalpha1-2Man functionalized G(3) and G(4)-PAMAM dendrimers have been synthesized and characterized by MALDI-TOF MS and NMR spectroscopy. Precipitation assays to assess the binding of the dimannose-functionalized dendrimers to Cyanovirin-N, a HIV-inactivating protein that blocks virus-to-cell fusion through high mannose mediated interactions, are presented.
Journal of the American Chemical Society, 2003
Protein-carbohydrate interactions play a critical role in many biological recognition events. Mul... more Protein-carbohydrate interactions play a critical role in many biological recognition events. Multivalent therapeutic agents that utilize protein-carbohydrate interactions have proven difficult to design, primarily because the fundamental requirements of protein-carbohydrate interactions are not well understood. Here, we report a systematic study of the effect on lectin binding of varying the loading of mannose surface residues on generations three through six PAMAM dendrimers. The degree of mannose functionalization was controlled by stoichiometric addition, and dendrimers were characterized using NMR and MALDI-TOF MS. Hemagglutination assays and quantitative precipitation assays were performed to determine the relative activity of the dendrimers. Using the mannose/hydroxyl-functionalized dendrimers reported here, we could systematically control both the degree of lectin clustering and the overall activity of the lectin with the dendrimer.
Carbohydrate Research, 2012
InCl 3 , InBr 3 , and In(OTf) 3 were tested as promoters in the preparation of glycosides from tr... more InCl 3 , InBr 3 , and In(OTf) 3 were tested as promoters in the preparation of glycosides from trichloroacetimidate precursors. A range of protecting groups and of alcohol acceptors were used to determine the versatility of these promoters. Disaccharide formation was demonstrated. In most cases, the In(III) compounds were shown to promote glycosylation better than the widely used promoter BF 3 •OEt 2 .
Bioorganic & Medicinal Chemistry Letters, 2011
The development of methodology that is designed to allow a significant increase in the patterning... more The development of methodology that is designed to allow a significant increase in the patterning and in the functionalization of the dendrimer is the ultimate goal of the research described here. Glycoside clusters based on TRIS were formed using click chemistry and were attached to PAMAM dendrimers. A series of dendrimers bearing tris-mannoside and an ethoxyethanol group was synthesized, and the binding interactions of these dendrimers with Concanavalin A were evaluated using inhibition ELISAs. The results of the inhibition ELISAs suggest that trismannoside clusters can replace individual sugars on the dendrimer without loss of function. Since tris-mannoside clustering allows for a redistribution of the dendrimers' surface functionalities, from this chemistry one can envision patterned dendrimers that incorporate multiple groups to increase the function and utility of the dendrimer.
Org. Biomol. Chem., 2004
Mannose-TEMPO functionalized G4-PAMAM dendrimers with increasing mannose loadings have been synth... more Mannose-TEMPO functionalized G4-PAMAM dendrimers with increasing mannose loadings have been synthesized and characterized by MALDI-TOF MS and EPR spectroscopy. Analysis of linebroadening effects in the EPR spectra of these dendrimers allowed us to determine the relative presentation of mannose and TEMPO on the dendrimer surface. Hemagglutination assays and affinity chromatography/EPR experiments to assess the activity of the mannose-TEMPO dendrimers with Concanavalin A are presented.
Organic and Biomolecular Chemistry, 2004
Mannose-TEMPO functionalized G4-PAMAM dendrimers with increasing mannose loadings have been synth... more Mannose-TEMPO functionalized G4-PAMAM dendrimers with increasing mannose loadings have been synthesized and characterized by MALDI-TOF MS and EPR spectroscopy. Analysis of linebroadening effects in the EPR spectra of these dendrimers allowed us to determine the relative presentation of mannose and TEMPO on the dendrimer surface. Hemagglutination assays and affinity chromatography/EPR experiments to assess the activity of the mannose-TEMPO dendrimers with Concanavalin A are presented.
Journal of Physical Chemistry B, Oct 20, 2005
Macromolecules, Mar 29, 2007
... J. Singel, and Mary J. Cloninger*. Department of Chemistry and Biochemistry and Center for Bi... more ... J. Singel, and Mary J. Cloninger*. Department of Chemistry and Biochemistry and Center for Bioinspired Nanomaterials, Montana State University, 108 Gaines Hall, Bozeman, Montana 59717. ... f) Bosman, AW; Jannsen, RAJ; Meijer, EW Macromolecules1997, 30, 3606−3611. ...
Molecular Pharmaceutics, Oct 4, 2016
The development of pathogenic bacteria resistant to current treatments is a major issue facing th... more The development of pathogenic bacteria resistant to current treatments is a major issue facing the world today. Here, the synthesis and biological activity of fourth generation poly(amidoamine) dendrimers decorated with 1-hexadecyl-azoniabicylo[2.2.2]octane (C 16-DABCO), a quaternary ammonium compound known to have antibacterial activity, are described. This highly cationic dendrimer antibiotic was tested against several Gram positive and Gram negative strains of pathogenic bacteria and exhibited activity against both. Higher activity toward the Gram positive strains that were tested was observed. After the antimicrobial activity was assessed, E. coli and B. cereus were subjected to a resistance selection study. This study demonstrated that a multivalent approach to antimicrobial design significantly reduces the likelihood of developing bacterial resistance. Highly cationic dendrimers were also used as pretreatment of a membrane in order to prevent biofilm formation.
International Journal of Molecular Sciences, 2016
Current opinion in drug discovery & development, 2002
Significant timely advances have been made in the synthesis of heterogeneously functionalized den... more Significant timely advances have been made in the synthesis of heterogeneously functionalized dendrimers. Convergent, divergent and other functionalization techniques have been used to create a variety of complex dendrimer motifs with more than one type of surface group. Synthetic advances, as well as pertinent applications of heterogeneously functionalized dendrimers, are reviewed.
ChemBioChem, 2014
By using lactose-functionalized poly(amidoamine) dendrimers as a tunable multivalent platform, we... more By using lactose-functionalized poly(amidoamine) dendrimers as a tunable multivalent platform, we studied cancer cell aggregation in three different cell lines (A549, DU-145, and HT-1080) with galectin-3. We found that small lactose-functionalized G(2)-dendrimer 1 inhibited galectin-3induced aggregation of the cancer cells. In contrast, dendrimer 4 (a larger, generation 6 dendrimer with 100 carbohydrate end groups) caused cancer cells to aggregate through a galectin-3 pathway. This study indicates that inhibition of cellular aggregation occurred because 1 provided competitive binding sites for galectin-3 (compared to its putative cancer cell ligand, TF-antigen on MUC1). Dendrimer 4, in contrast, provided an excess of ligands for galectin-3 binding; this caused crosslinking and aggregation of cells to be increased.
The Journal of Physical Chemistry B, 2011
The Journal of Physical Chemistry B, 2005
Starburst dendrimers are receiving considerable attention as templates for the assembly of struct... more Starburst dendrimers are receiving considerable attention as templates for the assembly of structured arrays of molecular components. This research motivates the development of improved methods for dendrimer characterizationsspecifically, for determining the numbers, distributions of numbers, and spatial distribution of molecular species synthetically attached to macromolecular templates. Such information provides the basis for advancing strategies aimed at controlling dendrimer functionalization, and thus represents enabling technology for tailoring the composition and structure of molecular arrays fashioned on dendrimer templates. Moreover, this information is vital to the proper interpretation of ongoing experiments in which dendrimers sparsely functionalized with reporter groups are used as probes. In this article, we report MALDI-TOF mass spectrometry and EPR spectroscopy of heterogeneously functionalized G(4)-PAMAM dendrimers bearing nitroxide spin-labels.
Organic & Biomolecular Chemistry, 2005
Manalpha1-2Man functionalized G(3) and G(4)-PAMAM dendrimers have been synthesized and characteri... more Manalpha1-2Man functionalized G(3) and G(4)-PAMAM dendrimers have been synthesized and characterized by MALDI-TOF MS and NMR spectroscopy. Precipitation assays to assess the binding of the dimannose-functionalized dendrimers to Cyanovirin-N, a HIV-inactivating protein that blocks virus-to-cell fusion through high mannose mediated interactions, are presented.
Journal of the American Chemical Society, 2003
Protein-carbohydrate interactions play a critical role in many biological recognition events. Mul... more Protein-carbohydrate interactions play a critical role in many biological recognition events. Multivalent therapeutic agents that utilize protein-carbohydrate interactions have proven difficult to design, primarily because the fundamental requirements of protein-carbohydrate interactions are not well understood. Here, we report a systematic study of the effect on lectin binding of varying the loading of mannose surface residues on generations three through six PAMAM dendrimers. The degree of mannose functionalization was controlled by stoichiometric addition, and dendrimers were characterized using NMR and MALDI-TOF MS. Hemagglutination assays and quantitative precipitation assays were performed to determine the relative activity of the dendrimers. Using the mannose/hydroxyl-functionalized dendrimers reported here, we could systematically control both the degree of lectin clustering and the overall activity of the lectin with the dendrimer.
Carbohydrate Research, 2012
InCl 3 , InBr 3 , and In(OTf) 3 were tested as promoters in the preparation of glycosides from tr... more InCl 3 , InBr 3 , and In(OTf) 3 were tested as promoters in the preparation of glycosides from trichloroacetimidate precursors. A range of protecting groups and of alcohol acceptors were used to determine the versatility of these promoters. Disaccharide formation was demonstrated. In most cases, the In(III) compounds were shown to promote glycosylation better than the widely used promoter BF 3 •OEt 2 .
Bioorganic & Medicinal Chemistry Letters, 2011
The development of methodology that is designed to allow a significant increase in the patterning... more The development of methodology that is designed to allow a significant increase in the patterning and in the functionalization of the dendrimer is the ultimate goal of the research described here. Glycoside clusters based on TRIS were formed using click chemistry and were attached to PAMAM dendrimers. A series of dendrimers bearing tris-mannoside and an ethoxyethanol group was synthesized, and the binding interactions of these dendrimers with Concanavalin A were evaluated using inhibition ELISAs. The results of the inhibition ELISAs suggest that trismannoside clusters can replace individual sugars on the dendrimer without loss of function. Since tris-mannoside clustering allows for a redistribution of the dendrimers' surface functionalities, from this chemistry one can envision patterned dendrimers that incorporate multiple groups to increase the function and utility of the dendrimer.
Org. Biomol. Chem., 2004
Mannose-TEMPO functionalized G4-PAMAM dendrimers with increasing mannose loadings have been synth... more Mannose-TEMPO functionalized G4-PAMAM dendrimers with increasing mannose loadings have been synthesized and characterized by MALDI-TOF MS and EPR spectroscopy. Analysis of linebroadening effects in the EPR spectra of these dendrimers allowed us to determine the relative presentation of mannose and TEMPO on the dendrimer surface. Hemagglutination assays and affinity chromatography/EPR experiments to assess the activity of the mannose-TEMPO dendrimers with Concanavalin A are presented.