RESUMO
To preorganize PNA for duplex formation, a new cyclic pyrrolidinone PNA analogue has been designed. In this analogue the aminoethylglycine backbone and the methylenecarbonyl linker are connected, introducing two chiral centers compared to PNA. The four stereoisomers of the adenine analogue were synthesized, and the hybridization properties of PNA decamers containing one analogue were measured against complementary DNA, RNA, and PNA strands. The (3S,5R) isomer was shown to have the highest affinity toward RNA, and to recognize RNA and PNA better than DNA. The (3S,5R) isomer was used to prepare a fully modified decamer which bound to rU10 with only a small decrease in Tm (delta Tm/mod = 1 degree C) relative to aminoethylglycine PNA.
Assuntos
Conformação de Ácido Nucleico , Ácidos Nucleicos Peptídicos/síntese química , Pirrolidinonas/química , Espectroscopia de Ressonância Magnética , Ácidos Nucleicos Peptídicos/química , Espectrometria de Massas de Bombardeamento Rápido de ÁtomosRESUMO
A patient with carbohydrate-deficient glycoprotein syndrome type 1b (CDGS1b) is reported. The patient presented at 5 months of age with failure to thrive, prolonged diarrhoea, hepatomegaly and elevated serum liver transaminases. Liver biopsy showed steatosis. A low serum albumin and elevated serum liver transaminases persisted throughout childhood during which he had repeated infectious illnesses. From the age of 10 years he had oesophageal and duodenal ulceration together with recurrent bacterial cholangitis. Liver biopsy demonstrated hepatic fibrosis. CDGS1b was suspected, supported by the finding of a protein-losing enteropathy and finally confirmed by showing a reduced phosphomannoseisomerase activity. This case illustrates a rare condition with a wide range of presentations.
Assuntos
Defeitos Congênitos da Glicosilação/diagnóstico , Manose-6-Fosfato Isomerase/deficiência , Manose/uso terapêutico , Adolescente , Defeitos Congênitos da Glicosilação/tratamento farmacológico , Defeitos Congênitos da Glicosilação/enzimologia , Diagnóstico Diferencial , Humanos , Lactente , Masculino , Manose-6-Fosfato Isomerase/biossíntese , Resultado do TratamentoRESUMO
Environmental conditions play an important role in conceptual studies of prebiotically relevant chemical reactions that could have led to functional biomolecules. The necessary source compounds are likely to have been present in dilute solution, raising the question of how to achieve selective concentration and to reach activation. With the assumption of an initial 'RNA World', the questions of production, concentration, and interaction of aldehydes and aldehyde phosphates, potential precursors of sugar phosphates, come into the foreground. As a possible concentration process for simple, uncharged aldehydes, we investigated their adduct formation with sulfite ion bound in the interlayer of positively charged expanding-sheet-structure double-layer hydroxide minerals. Minerals of this type, initially with chloride as interlayer counter anion, have previously been shown to induce concentration and subsequent aldolization of aldehyde phosphates to form tetrose, pentose, and hexose phosphates. The reversible uptake of the simple aldehydes formaldehyde, glycolaldehyde, and glyceraldehyde by adduct formation with the immobilized sulfite ions is characterized by equilibrium constants of K=1.5, 9, and 11, respectively. This translates into an observable uptake at concentrations exceeding 50 mM.
Assuntos
Aldeídos/química , Hidróxido de Alumínio/química , Evolução Química , Hidróxido de Magnésio/química , Fosfatos Açúcares/síntese química , Acetaldeído/análogos & derivados , Acetaldeído/síntese química , Acetaldeído/química , Aldeídos/síntese química , Hidróxido de Alumínio/síntese química , Ânions , Evolução Molecular , Exobiologia , Formaldeído/síntese química , Formaldeído/química , Gliceraldeído/síntese química , Gliceraldeído/química , Hidróxidos/química , Hidróxido de Magnésio/síntese química , Minerais/química , Fosfatos Açúcares/química , Sulfitos/químicaRESUMO
A solid-phase method for the introduction of a variety of different side chains into oligoribonucleotides is presented. It is based on a beta-D-allofuranosyl phosphoramidite with a bromopentyl-substituent tethered to the 6'-O position. After its incorporation into fully protected, immobilized RNA sequences, the bromine was substituted with a variety of soft nucleophiles which, in some cases, allowed further transformations. After deprotection and detachment, the corresponding functionalized oligoribonucleotides were purified and characterized. Incorporation of such side chains led to a slight lowering of transition temperatures, but some of them led to a significant enthalpic stabilization of an A-type RNA duplex.
Assuntos
Glicoconjugados/química , Oligorribonucleotídeos/química , Amidas/química , Sequência de Bases , Bromo/química , Cromatografia Líquida de Alta Pressão , Citosina/análogos & derivados , Citosina/química , Estabilidade de Medicamentos , Espectrometria de Massas , Estrutura Molecular , Ácidos Fosfóricos/química , RNA/química , TermodinâmicaRESUMO
Formation of rac.-pentose-2,4-bisphosphates is demonstrated, starting from glycolaldehyde phosphate and glyceraldehyde-2-phosphate, and induced by mixed valence double layer metal hydroxide minerals. The reactions proceed from dilute aqueous reactant solutions (1.5 mM) at near neutral pH. Conditions have been established, where ribose-2,4-bisphosphate is the major product (approximately 48%) among the pentose-2,4-bisphosphates, which are formed with up to 25% yield.
Assuntos
Pentosefosfatos/síntese química , Hidróxido de Alumínio , Cátions Bivalentes , Cromatografia Gasosa-Espectrometria de Massas , Gliceraldeído 3-Fosfato , Concentração de Íons de Hidrogênio , Hidróxido de Magnésio , Espectroscopia de Ressonância Magnética , Minerais , Pentosefosfatos/química , Soluções , Temperatura , ÁguaRESUMO
The oligomerization of activated D- and L- and racemic guanosine-5'-phosphoro-2-methylimidazole on short templates containing D- and L-deoxycytidylate has been studied. Results obtained with D-oligo(dC)s as templates are similar to those previously reported for experiments with a poly(C) template. When one L-dC or two consecutive L-dCs are introduced into a D-template, regiospecific synthesis of 3'-5' oligo(G)s proceeds to the end of the template, but three consecutive L-dCs block synthesis. Alternating D-,L-oligomers do not facilitate oligomerization of the D-, L-, and racemic 2-guanosine-5'-phosphoro-2-methylimidazole. We suggest that once a "predominately D-metabolism" existed, occasional L-residues in a template would not have led to the termination of self-replication.
Assuntos
Guanosina/química , Oligonucleotídeos/química , Dimerização , Moldes GenéticosRESUMO
A method for the facile preparation of oligoribonucleotide analogues containing beta-d-allofuranosyl nucleosides with additional functional groups tethered to the 6'-O positions is presented. It is based on the synthesis of two protected nucleosides carrying a 6'-O -bromopentyl and a 6'-O -methylaminopentyl substituent. By a simple two-step procedure, these key intermediates were transformed into two phosphoramidites carrying a 1-aza-18-crown-6 and a triethyleneglycol group, respectively, each capable of complexing metal ions. By automated synthesis, these functionalized nucleoside analogues were efficiently incorporated into short oligoribonucleotides. Under physiological conditions (150 mM NaCl, 2 mM MgCl2, pH 7.4), incorporation of a single allofuranosyl cytosine substituted with a triethyleneglycol moiety led to a significant enthalpic stabilization of an A-type RNA duplex. This observation is in agreement with a metal ion-mediated stabilizing interaction between the two pairing strands.
Assuntos
Citosina/análogos & derivados , Citosina/química , Oligorribonucleotídeos/química , Oligorribonucleotídeos/síntese química , Sítios de Ligação , Metais/química , Estrutura MolecularRESUMO
We report a search in cold, quiescent and in 'hot core' type interstellar molecular clouds for the small cyclic molecule oxiranecarbonitrile (C3H3NO), which has been suggested as a precursor of important prebiotic molecules. We have determined upper limits to the column density and fractional abundance for the observed sources and find that, typically, the fractional abundance by number relative to molecular hydrogen of C3H3NO is less than a few times 10(-10). This limit is one to two orders of magnitude less than the measured abundance of such similarly complex species as CH3CH2CN and HCOOCH3 in well-studied hot cores. A number of astrochemical discoveries were made, including the first detection of the species CH3CH2CN in the massive star-forming clouds G34.3+0.2 and W51M and the first astronomical detections of some eight rotational transitions of CH3CH2CN, CH3CCH, and HCOOCH3. In addition, we found 8 emission lines in the 89 GHz region and 18 in the 102 GHz region which we were unable to assign.
Assuntos
Astronomia/métodos , Óxido de Etileno/análogos & derivados , Evolução Química , Meio Ambiente Extraterreno , Óxido de Etileno/análise , Temperatura Alta , Compostos Orgânicos , Origem da VidaRESUMO
Glycolaldehyde phosphate, sorbed from highly dilute, weakly alkaline solution into the interlayer of common expanding sheet structure metal hydroxide minerals, condenses extensively to racemic aldotetrose-2,4-diphosphates and aldohexose-2,4,6-triphosphates. The reaction proceeds mainly through racemic erythrose-2,4-phosphate, and terminates with a large fraction of racemic altrose-2,4,6-phosphate. In the absence of an inductive mineral phase, no detectable homogeneous reaction takes place in the concentration- and pH range used. The reactant glycolaldehyde phosphate is practically completely sorbed within an hour from solutions with concentrations as low as 50 micrometers; the half-time for conversion to hexose phosphates is of the order of two days at room temperature and pH 9.5. Total production of sugar phosphates in the mineral interlayer is largely independent of the glycolaldehyde phosphate concentration in the external solution, but is determined by the total amount of GAP offered for sorption up to the capacity of the mineral. In the presence of equimolar amounts of rac-glyceraldehyde-2-phosphate, but under otherwise similar conditions, aldopentose-2,4,-diphosphates also form, but only as a small fraction of the hexose-2,4,6-phosphates.