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1.
Mol Cell Biol ; 21(1): 156-63, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11113190

RESUMO

Nearly 40% of cases of acute myelogenous leukemia (AML) of the M2 subtype are due to a chromosomal translocation that combines a sequence-specific DNA binding protein, AML1, with a potent transcriptional repressor, ETO. ETO interacts with nuclear receptor corepressors SMRT and N-CoR, which recruit histone deacetylase to the AML1-ETO oncoprotein. SMRT-N-CoR interaction requires each of two zinc fingers contained in C-terminal Nervy homology region 4 (NHR4) of ETO. However, here we show that polypeptides containing NHR4 are insufficient for interaction with SMRT. NHR2 is also required for SMRT interaction and repression by ETO, as well as for inhibition of hematopoietic differentiation by AML1-ETO. NHR2 mediates oligomerization of ETO as well as AML1-ETO. Fusion of NHR4 polypeptide to a heterologous dimerization domain allows strong interaction with SMRT in vitro. These data support a model in which NHR2 and NHR4 have complementary functions in repression by ETO. NHR2 functions as an oligomerization domain bringing together NHR4 polypeptides that together form the surface required for high-affinity interaction with corepressors. As nuclear receptors also interact with corepressors as dimers, oligomerization may be a common mechanism regulating corepressor interactions.


Assuntos
Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogênicas , Proteínas Repressoras/metabolismo , Fatores de Transcrição/química , Fatores de Transcrição/metabolismo , Sítios de Ligação , Diferenciação Celular , Proteínas de Ligação a DNA/genética , Dimerização , Hematopoese , Humanos , Correpressor 1 de Receptor Nuclear , Correpressor 2 de Receptor Nuclear , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo , Ligação Proteica , Estrutura Quaternária de Proteína , Estrutura Terciária de Proteína , Proteína 1 Parceira de Translocação de RUNX1 , Receptores Citoplasmáticos e Nucleares/metabolismo , Deleção de Sequência , Fatores de Transcrição/genética , Transfecção , Células U937 , Dedos de Zinco
2.
Mol Cell ; 5(5): 811-20, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10882117

RESUMO

RAR and AML1 transcription factors are found in leukemias as fusion proteins with PML and ETO, respectively. Association of PML-RAR and AML1-ETO with the nuclear corepressor (N-CoR)/histone deacetylase (HDAC) complex is required to block hematopoietic differentiation. We show that PML-RAR and AML1-ETO exist in vivo within high molecular weight (HMW) nuclear complexes, reflecting their oligomeric state. Oligomerization requires PML or ETO coiled-coil regions and is responsible for abnormal recruitment of N-CoR, transcriptional repression, and impaired differentiation of primary hematopoietic precursors. Fusion of RAR to a heterologous oligomerization domain recapitulated the properties of PML-RAR, indicating that oligomerization per se is sufficient to achieve transforming potential. These results show that oligomerization of a transcription factor, imposing an altered interaction with transcriptional coregulators, represents a novel mechanism of oncogenic activation.


Assuntos
Transformação Celular Neoplásica , Leucemia/genética , Proteínas de Neoplasias/metabolismo , Proteínas de Fusão Oncogênica/metabolismo , Fatores de Transcrição/metabolismo , Subunidade alfa 2 de Fator de Ligação ao Core , Histona Desacetilases/metabolismo , Humanos , Leucemia/etiologia , Leucemia Mieloide/etiologia , Leucemia Mieloide/genética , Leucemia Promielocítica Aguda/etiologia , Leucemia Promielocítica Aguda/genética , Proteínas Nucleares/metabolismo , Correpressor 1 de Receptor Nuclear , Fragmentos de Peptídeos/metabolismo , Ligação Proteica , Estrutura Quaternária de Proteína , Proteína 1 Parceira de Translocação de RUNX1 , Proteínas Repressoras/metabolismo , Elementos de Resposta , Transcrição Gênica , Tretinoína
4.
J Biol Chem ; 271(30): 17804-10, 1996 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-8663266

RESUMO

Samples of heparan sulfate, isolated from bovine aorta, lung, intestine, and kidney, were degraded by digestion with a mixture of heparitinases or by treatment with nitrous acid, with or without previous N-deacetylation. Analysis of the resulting oligosaccharides showed that the various heparan sulfate samples all contained regions of up to 8 or 9 consecutive N-acetylated glucosamine residues, as well as contiguous N-sulfated sequences. L-Iduronic acid accounted for a remarkably constant proportion, 50-60%, of the total hexuronic acid units within the latter structures. Of the total iduronic acid units, 36-55% were located outside the contiguous N-sulfated regions, presumably in sequences composed of alternating N-acetylated and N-sulfated disaccharide residues. While most of the iduronic acid units within the N-sulfated blocks were 2-O-sulfated, those located outside were almost exclusively nonsulfated. The heparan sulfate preparations differed markedly with regard to the content of 6-O-sulfated glucosamine units, more than half of which were located outside the N-sulfated block regions. These findings suggest that the formation of iduronic acid residues and their subsequent 2-O-sulfation are coupled within but not outside the contiguous N-sulfated regions of the heparan sulfate chains and, furthermore, that the 2-O- and 6-O-sulfotransferase reactions are differentially regulated during heparan sulfate biosynthesis.


Assuntos
Aorta/química , Heparitina Sulfato/química , Intestinos/química , Rim/química , Pulmão/química , Animais , Configuração de Carboidratos , Sequência de Carboidratos , Bovinos , Dissacarídeos/química , Dados de Sequência Molecular , Análise de Sequência
5.
J Biol Chem ; 271(4): 2243-8, 1996 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-8567685

RESUMO

Heparin-binding growth-associated molecule (HB-GAM) is a cell-surface- and extracellular matrix-associated protein that lines developing axons in vivo and promotes neurite outgrowth in vitro. Because N-syndecan (syndecan-3) was found to function as a receptor in HB-GAM-induced neurite outgrowth, we have now studied whether the heparan sulfate side chains of N-syndecan play a role in HB-GAM-neuron interactions. N-Syndecan from postnatal rat brain was found to inhibit HB-GAM-induced but not laminin-induced neurite outgrowth when added to the assay media. The inhibitory activity was abolished by treating N-syndecan with heparitinase, but it was retained in N-syndecan-derived free glycosaminoglycan chains, suggesting that N-syndecan heparan sulfate at the cell surface is involved in HB-GAM-induced neurite outgrowth. Binding to HB-GAM and inhibition of neurite outgrowth was observed with heparin-related polysaccharides only; galactosaminoglycans were inactive. Significant inhibition of neurite outgrowth was induced by heparin and by N-syndecan heparan sulfate but not by heparan sulfates from other sources. A minimum of 10 monosaccharide residues were required for HB-GAM-induced neurite outgrowth. Experiments with selectively desulfated heparins indicated that 2-O-sulfated iduronic acid units, in particular, are of importance to the interaction with HB-GAM, were implicated to a lesser extent. Structural analysis of N-syndecan from 6-day-old rat brain indicated that the heparan sulfate chains contain sequences of contiguous, N-sulfated disaccharide units with an unusually high proportion (82%) of 2-O-sulfated iduronic acid residues. We suggest that this property of N-syndecan heparan sulfate is essential for HB-GAM binding and induction of neurite outgrowth.


Assuntos
Proteínas de Transporte/metabolismo , Citocinas/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neuritos/ultraestrutura , Proteoglicanas/metabolismo , Animais , Ligação Competitiva , Encéfalo/embriologia , Encéfalo/ultraestrutura , Células Cultivadas , Heparitina Sulfato/metabolismo , Oligossacarídeos/química , Polissacarídeos/química , Ratos , Proteínas Recombinantes , Sindecana-3
6.
J Biol Chem ; 270(52): 31303-9, 1995 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-8537400

RESUMO

Immunohistochemical application of antibodies against heparan sulfate proteoglycan core protein and heparitinase-digested heparan sulfate stubs showed the presence of heparan sulfate proteoglycan in all basement membranes of the rat kidney. However, a monoclonal antibody (JM-403) against native heparan sulfate (van den Born, J., van den Heuvel, L. P. W. J., Bakker, M. A. H., Veerkamp, J. H., Assmann, K. J. M., and Berden, J. H. M. (1992) Kidney Int. 41, 115-123) largely failed to stain tubular basement membranes, suggesting the presence of heparan sulfate chains lacking the specific JM-403 epitope. Heparan sulfate preparations from various sources differed markedly with regard to JM-403 binding, as demonstrated by liquid phase inhibition in enzyme-linked immunosorbent assay, the interaction decreasing with increasing sulfate contents of the polysaccharide. Mapping of the JM-403 epitope indicated that it was dominated by one or more N-unsubstituted glucosamine unit(s), since treatments that destroyed or altered the structure of such units in heparan sulfate preparations (cleavage at N-unsubstituted glucosamine units with HNO2 at pH 3.9 and N-acetylation with acetic anhydride, respectively), abolished antibody binding. Conversely, immunoreactivity could be induced in a (D-glucuronyl-1,4-N-acetyl-D-glucosaminyl-1,4) polysaccharide by the generation of N-unsubstituted glucosamine N-unsubstituted glucosamine in a JM-403-binding heparan sulfate (preparation HS-II from human aorta) was demonstrated by an approximately 3-fold reduction in molecular size following HNO2 (pH 3.9) treatment. Further characterization of the epitope recognized by JM-403, based on enzyme-linked immunosorbent assay inhibition tests with chemically/enzymatically modified polysaccharides, indicated that one or more N-sulfated glucosamine units are invariable present, whereas L-iduronic acid and O-sulfate residues appear to inhibit JM-403 reactivity. It is concluded that the epitope contains one or more N-unsubstituted glucosamine and D-glucuronic acid units and is located in a region of the heparan sulfate chain composed of mixed N-sulfated and N-acetylated disaccharide units.


Assuntos
Anticorpos Monoclonais/imunologia , Glucosamina/análise , Heparitina Sulfato/química , Animais , Bovinos , Epitopos/imunologia , Escherichia coli/química , Heparina/química , Heparina/imunologia , Heparitina Sulfato/imunologia , Humanos , Polissacarídeos Bacterianos/imunologia , Ratos , Suínos
7.
J Biol Chem ; 269(47): 29867-73, 1994 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-7961981

RESUMO

Heparin binds to phospholipase A2 myotoxins from Bothrops asper snake venom, inhibiting their toxic activities. This interaction was investigated using purified myotoxin II, a Lys-49 phospholipase A2 of this venom, and a series of heparin variants, fragments, and other glycosaminoglycans. The binding was correlated to toxin neutralization, using endothelial cells as a target. Myotoxin II binds radiolabeled heparin in solution unselectively, and forms macromolecular complexes with an optimum at a heparin:toxin molar ratio of 1:5. Both O-sulfates and N-sulfates play a role in heparin binding, in the order of importance 2-O-sulfates > 6-Osulfates > N-sulfates. The shortest heparin oligosaccharides interacting with myotoxin II are hexasaccharides. The binding of a neutralizing monoclonal antibody (MAb-3) to myotoxin II was not inhibited by heparin, indicating that the two molecules interact with different sites on the toxin. A synthetic peptide (residues 115-129 in the numbering system of Renetseder et al. (Renetseder, R., Brunie, S., Dijkstra, B. W., Drenth, J., and Sigler, P. B. (1985) J. Biol. Chem. 260, 11627-11634) of myotoxin II displays both heparin-binding and cytolytic activities. It is concluded that heparin neutralizes myotoxin II by binding to a strongly cationic site in the region of residues 115-129, a possible contribution of lysines 36 and 38 suggested by molecular modeling studies. As this cationic region appears to be responsible for the cytolytic activity of the toxin, the present report constitutes the first identification of a cytotoxic region on a phospholipase A2 myotoxin.


Assuntos
Venenos de Crotalídeos/enzimologia , Heparina/metabolismo , Lisina/metabolismo , Neurotoxinas/metabolismo , Fosfolipases A/metabolismo , Sequência de Aminoácidos , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Fosfolipases A2 do Grupo II , Modelos Moleculares , Dados de Sequência Molecular , Neurotoxinas/toxicidade , Fosfolipases A/química , Fosfolipases A2 , Ligação Proteica , Proteínas de Répteis , Suínos
8.
J Biol Chem ; 269(40): 24538-41, 1994 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-7929122

RESUMO

O-Sulfotransferases involved in heparin biosynthesis were purified > or = 10,000-fold from detergent extracts of mouse mastocytoma tissue by sequential chromatographies on DEAE-Sephacel, heparin-agarose, blue Sepharose, and 3',5'-ADP-Sepharose. The resultant preparation catalyzed the transfer of 35S from 3'-phosphoadenosyl-5'-phospho-[35S]sulfate into N,O-desulfated, re-N-sulfated heparin. Anion-exchange high performance liquid chromatography of disaccharides obtained by deaminative cleavage of the 35S-labeled polysaccharide product revealed O-35S-sulfation at C-2 of L-iduronic acid and at C-6 of D-glucosamine units. SDS-polyacrylamide gel electrophoresis of semipurified enzyme followed by extraction of gel segments and renaturation of proteins consistently showed two distinct fractions of O-sulfotransferase activity, corresponding to proteins of approximately 20 and approximately 60 kDa. The approximately 60-kDa enzyme(s) catalyzed both the 2-O- and 6-O-sulfotransferase reactions, whereas the approximately 20-kDa fraction promoted iduronosyl 2-O-sulfation only. These results are discussed in relation to previous findings, indicating that some of the enzymes involved in heparin biosynthesis catalyze more than one reaction.


Assuntos
Heparina/biossíntese , Sulfotransferases/isolamento & purificação , Animais , Sequência de Carboidratos , Sarcoma de Mastócitos/enzimologia , Camundongos , Dados de Sequência Molecular , Sulfotransferases/metabolismo
9.
J Biol Chem ; 269(20): 14451-6, 1994 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-8182050

RESUMO

Heparin is a sulfated glycosaminoglycan, synthesized by connective tissue-type mast cells. Rat mast cell protease 1 (RMCP-1), a chymotrypsin-like serine protease expressed specifically by connective tissue-type mast cells, is recovered in a macromolecular complex with heparin proteoglycan. The heparin.RMCP-1 complexes are stored in the secretory granules of the cells and are released following mast cell activation. We showed previously that dissociation of RMCP-1 from heparin resulted in loss of protease activity, as measured by its ability to inactivate thrombin. In the present report the binding of heparin to RMCP-1 was characterized. Affinity chromatography on heparin-Sepharose showed that RMCP-1 displayed high affinity for heparin, with approximately 1.2 M NaCl being required for elution of RMCP-1 from the affinity matrix. The structural requirements for the binding of heparin to RMCP-1 were investigated. Heparan sulfate, chondroitin sulfate, and dermatan sulfate, three glycosaminoglycans structurally related to heparin, were > or = 80-fold less effective in binding to RMCP-1 than heparin. The 2-O-sulfate, 6-O-sulfate, and N-sulfate groups in heparin were all shown to contribute in the binding. The minimal heparin sequence required for binding to RMCP-1 was found in a 14-saccharide fraction. 14-Saccharide species, obtained after separation by anion exchange chromatography, showed continuously increased binding with increasing anionic charge densities. The 16-18-saccharides were the smallest heparin oligosaccharides capable of accelerating the inactivation of thrombin by RMCP-1.


Assuntos
Heparina/metabolismo , Oligossacarídeos/metabolismo , Serina Endopeptidases/metabolismo , Animais , Sequência de Carboidratos , Bovinos , Quimases , Dissacarídeos/química , Dissacarídeos/isolamento & purificação , Glicosaminoglicanos/metabolismo , Heparina/química , Heparina/isolamento & purificação , Mucosa Intestinal , Cinética , Dados de Sequência Molecular , Oligossacarídeos/isolamento & purificação , Ratos , Especificidade por Substrato , Suínos , Trombina/metabolismo
11.
J Biol Chem ; 268(32): 23898-905, 1993 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-8226930

RESUMO

Experiments based on interaction in free solution between basic fibroblast growth factor (FGF-2) and saccharides related to heparin/heparan sulfate showed that the growth factor binds to heparin and to selectively glucosaminyl 6-O-desulfated heparin but poorly to iduronosyl 2-O-desulfated heparin. 2-O-sulfate groups thus are essential to the interaction, whereas 6-O-sulfates are not required nor do they interfere with FGF-2 binding. Comparison of various bound/nonbound oligosaccharides implicated a minimal pentasaccharide sequence for FGF-2 binding, with the structure: -hexuronic acid-glucosamine N-sulfate-hexuronic acid-glucosamine N-sulfate-iduronic acid 2-O-sulfate- (reducing terminus to the right). Such (overlapping) sequences are abundant in heparin, albeit heavily obscured by irrelevant O-sulfate groups, and occur also in heparan sulfate, with or without additional O-sulfates.


Assuntos
Fator 2 de Crescimento de Fibroblastos/metabolismo , Heparina/metabolismo , Heparitina Sulfato/metabolismo , Animais , Sítios de Ligação , Sequência de Carboidratos , Heparina/química , Heparitina Sulfato/química , Humanos , Dados de Sequência Molecular , Oligossacarídeos/metabolismo , Suínos
12.
J Biol Chem ; 268(32): 23906-14, 1993 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-7693696

RESUMO

Chlorate-treated Swiss 3T3 fibroblasts, with impaired synthesis of heparan sulfate proteoglycan, were used as target cells in assessing the ability of exogenous heparin-derived saccharides to promote the mitogenic activity of basic fibroblast growth factor 2 (FGF-2). Full-size native heparin (carrying iduronosyl 2-O-sulfate and glucosaminyl 6-O-sulfate groups), as well as a dodecasaccharide fraction isolated after limited deaminative cleavage of heparin, were efficient promoters, whereas the corresponding decasaccharides, or smaller oligosaccharides, were inactive. Neither selectively 2-O-desulfated nor preferentially 6-O-desulfated heparin were active. However, the latter derivative competed with native heparin for binding to FGF-2 and thus blocked the ability of native heparin to promote the mitogenic activity of FGF-2. The 6-O-desulfated heparin also prevented the ability of FGF-2 to suppress myogenic differentiation in MM14 mouse myoblasts. The binding region for FGF-2 has been identified as a pentasaccharide sequence containing a single essential O-sulfate group, at C2 of iduronic acid (1). It is proposed that the dodecasaccharide sequence required to promote receptor signaling by FGF-2 encompasses this pentasaccharide region, which binds the growth factor, and a site interacting with the receptor that contains essential 2-O- and 6-O-sulfate groups. Similar studies involving the related growth factors, FGF-1 and FGF-4, revealed differential effects of saccharides. The mitogenic effect induced by FGF-1 thus was not blocked by either the 2-O- or the 6-O-desulfated heparins. However, both of these derivatives, at high concentrations, promote mitogenic activity of FGF-4. It is concluded that specific saccharide sequences within heparan sulfate glycosaminoglycan chains favor the signaling by distinct members of the FGF family.


Assuntos
Fator 1 de Crescimento de Fibroblastos/metabolismo , Fator 2 de Crescimento de Fibroblastos/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Heparina/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Células 3T3 , Animais , Bovinos , Diferenciação Celular , Fator 1 de Crescimento de Fibroblastos/antagonistas & inibidores , Fator 2 de Crescimento de Fibroblastos/antagonistas & inibidores , Fator 4 de Crescimento de Fibroblastos , Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Heparina/química , Humanos , Camundongos , Músculos/citologia , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Transdução de Sinais
13.
Biochim Biophys Acta ; 1225(1): 57-63, 1993 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-7694658

RESUMO

Multiple interactions between human vitronectin and Staphylococcus aureus strain V8 were observed. An upward-curved Scatchard plot indicated both high-affinity binding (Kd1 = 7.4 x 10(-10) M) with 260 binding sites per bacterial cell and moderate-affinity binding (Kd2 = 7.4 x 10(-8) M) with 5240 copies per cell. Negative cooperativity of this binding was characterized by its Hill coefficient of less than unity (0.70 +/- 0.08). Up to 60% of the vitronectin-bacteria interaction was unaffected by high ionic strength (i.e., 2.4 M NaCl), and was not inhibited by highly-charged heparin oligosaccharides. Various oligosaccharides (4-20 monosaccharide units) generated by partial deaminative cleavage of heparin were found to affect vitronectin binding to S. aureus. Short-chain-length oligosaccharides increase and long oligosaccharides inhibit vitronectin binding, in accordance with direct association of these saccharides with multimeric vitronectin. A protein having a molecular mass of 60 kDa was identified as a putative high-affinity staphylococcal vitronectin-binding protein. These results indicate that interaction of multimeric vitronectin, mostly present at extracellular matrix sites with multiple recognition sites on the S. aureus surface, may contribute to bacterial colonisation.


Assuntos
Glicoproteínas/metabolismo , Staphylococcus aureus/metabolismo , Sítios de Ligação , Western Blotting , Glicoproteínas/isolamento & purificação , Humanos , Oligossacarídeos/metabolismo , Oligossacarídeos/farmacologia , Concentração Osmolar , Staphylococcus aureus/crescimento & desenvolvimento , Vitronectina
14.
Glycobiology ; 3(3): 271-7, 1993 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8358152

RESUMO

Platelet factor 4 (PF4) is a platelet-derived protein capable of binding to, and thus neutralizing, the biological activities of heparin and heparan sulphate. The mode of binding of PF4 to heparin was investigated in a comparative study also involving antithrombin (AT; previously shown to selectively bind a specific oligosaccharide sequence) and fibronectin (FN; non-specific electrostatic interaction). Heparin-derived saccharides were incubated with each of the three proteins, followed by separation of free and protein-bound carbohydrate on a nitrocellulose filter. The interaction systems involved either (i) competition for the protein ligand between 3H-labelled heparin and unlabelled, size-fractionated heparin oligosaccharides (isolated after deaminative cleavage with HNO2) or (ii) direct binding of 3H-labelled oligosaccharides. Species smaller than octasaccharides were unable to bind AT, whereas binding to FN and PF4 increased continuously throughout the series, with increasing size of the oligosaccharides. Further separation by anion-exchange chromatography showed that the PF4-binding and FN-binding octasaccharides represented essentially all components present in the initial octasaccharide fraction, the proportion of binding species increasing with charge (hence with the degree of sulphation). The AT-binding octasaccharides, on the other hand, selectively represented only a few of the total octasaccharide components, without any correlation to overall charge. These results indicate that the binding of PF4 to heparin occurs by relatively non-specific electrostatic interactions. The methodology delineated here may be generally useful in assessing specificity in glycosaminoglycan-protein interactions.


Assuntos
Antitrombinas/metabolismo , Heparina/metabolismo , Oligossacarídeos/metabolismo , Fator Plaquetário 4/metabolismo , Animais , Sequência de Carboidratos , Bovinos , Cromatografia por Troca Iônica , Fibronectinas/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Cinética , Dados de Sequência Molecular , Oligossacarídeos/isolamento & purificação , Ligação Proteica , Relação Estrutura-Atividade , Ácidos Sulfúricos/análise , Suínos , Trítio
15.
Carbohydr Res ; 244(2): 205-23, 1993 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-8348550

RESUMO

Derivatisation/FABMS strategies applicable to the structure analysis of low microgram quantities of heparin-derived oligosaccharides are described. Negative and positive FAB data from permethyl derivatives and positive FAB data from the products of subsequent methanolysis are reported for sulfated tetrasaccharides prepared by nitrous acid degradation of heparin. The preparation and FAB behaviour of acetylated derivatives of sulfated oligosaccharides are described for the first time, and the stability of the sulfate groups to base-catalysed acetylation is demonstrated. The acetylation/FABMS methodology, which yields high quality data, shows promise for the characterisation of a wide range of sulfated glycoconjugates.


Assuntos
Heparina/química , Oligossacarídeos/análise , Acetilação , Sequência de Carboidratos , Desaminação , Metanol/química , Metilação , Dados de Sequência Molecular , Estrutura Molecular , Espectrometria de Massas de Bombardeamento Rápido de Átomos
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