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Bioorganic Chemistry

Contributors: lmorgado

 

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Bioorganic Chemistry is the interface of organic chemistry and biology. Our research uses the principles and techniques of organic chemistry in attempting to solve problems of relevance to biology. We can design synthetic derivatives of natural products, that improve on nature.

 


 

Rita Ventura
Investigador Auxiliar
PhD 1999 in Chemistry, ITQB-UNL

Phone (+351) 214469775/78 | Extension 1775/1778
rventura@itqb.unl.pt

Lab Website

 
Research Interests

Our group is interested in the synthesis of small molecules that can act as catalysts without the addition of metals – organocatalysts. Organocatalysis can be utilised for the construction of enantiopure complex organic molecules, thus providing an alternative or a complement to organometallic and enzymatic catalysts. It is interesting to note that a simple aminoacid, proline, is an excellent organocatalyst for several transformations, emphasising the “greener” properties of organocatalyts compared with traditional ones. We prepared a range of structural related organocatalysts with variation of the configuration of key functional groups, which were also varied, and could draw interesting conclusions of the spacial and chemical features more determinant for the enantio- and diastereoselectivity outcome of the reactions studied.

Another area of interest is carbohydrate chemistry. One of our aims is to construct a library of carbohydrate derived hypersolutes using solid supported synthesis, which will provide us with a wide range of new compounds that will be tested by the Cell Physiology and NMR group for their ability to prevent protein aggregation and for protein thermostabilisation.
 We synthesised a series of chemical derivatives of mannose and glucose solutes, including dissacharides, some of which presented better thermostabilisation properties than the ones found in nature. In our studies, a new glucosyl donor was used as well as a much simpler glycosylation method that has afforded the desired alpha anomeric selectivity and avoided the need for using expensive reagents. The synthesis of new solutes, with more chalenging structures, are being synthesised in solution and in solid phase, requiring better glycosilation selectivities. Galactose derivatives are also being prepared.

Recently, we are also collaborating with the Bacterial Signaling group in the synthesis of AI-2, a quorum sensing autoinducer, well known for its ability to mediate inter-species communication regulating important bacterial group behaviors such as biofilm formation, virulence, and antibiotic production. We developed a new synthetic approach for synthesizing the precursor of AI-2, 4,5-dihydroxy-2,3-pentanedione (DPD). The new strategy will allow the preparation of labelled DPD and a wide range of new analogues with a side group other than methyl. The labelled DPD constitute an important reagent for the ongoing elucidation of the biochemical fate of this molecule at the cellular level and the production of DPD. A quantum dot (QD) will be linked to DPD to produce fluorescent labeled AI-2 (AI-2-QD), which will be a valuable tool to study several aspects of AI-2 signalling.

NOTE: AI-2 and related compounds are available for sale.

 

 

Group Members

  • Ana Sofia Miguel, Post-doc researcher
  • Eva Lourenço, PhD Student, co-supervisor: Helena Santos
  • Osvaldo Ascenso, Graduate Student
  • Raquel Araújo, Technician student

 

Selected Publications

  1. Rui, F.; Marques, J. C.; Miller, S. T.; Maycock, C. D.; Xavier, K. B.; Ventura, M. R. “Stereochemical diversity of AI-2 analogs modulates quorum sensing in Vibrio Harveyi and Escheria coli”, Bioorg. Med. Chem. 2012, 20, 249.
  2. Lourenço, E. C.; Ventura, M. R. “Synthesis of Potassium (2R)-2-O-α-D-Mannopyranosyl-(1→2)-α-Dglucopyranosyl-2,3-dihydroxypropanoate: A Naturally Compatible Solute”, Eur. J. Org. Chem. 2011, 6698.
  3. Ascenso, O. S.; Marques, J. C.; Santos, A. R.; Xavier, K. X.; Ventura, M. R.; Maycock, C. D. “An efficient synthesis of the precursor of AI-2, the signalling molecule for inter-species quorum sensing”, Bioorg. Med. Chem. 2011, 19, 1236.

 

Laboratory's Website

For further information please visit the laboratory's website

 

Química Bioorgânica (PT)

A Química Bioorgânica é a interface entre a química orgânica e a biologia. A nossa investigação usa os princípios e técnicas de química orgânica para tentar resolver problemas relevantes na área da biologia. Podemos também desenvolver derivados sintéticos com propriedades melhores que as correspondentes moléculas naturais, contribuíndo para melhorar e perceber a natureza.

O nosso grupo está interessado na síntese de moléculas pequenas que podem actuar como catalisadores – organocatalisadores – e que podem ser usados na construção de moléculas orgânicas enantiopuras, sendo uma alternativa aos catalisadores contendo metais e enzimas.

Outra área de investigação no nosso grupo é a química de carbohidratos. Um dos objectivos é sintetisar uma grande variedade de derivados de hipersolutos, usando síntese em suporte sólido e síntese paralela, que serão testados no grupo de Fisiologia Celular e RMN como inibidores de agregação proteíca e como termoestabilisadores de proteínas. Em colaboração com o grupo de Sinalização Bacteriana, desenvolvemos uma síntese eficiente da 4,5-dihidroxi-2,3-pentanodiona (DPD), precursor do AI-2, um autoindutor de “detecção de quorum” que regula a comunicação inter-espécies entre bactérias, processo responsável por comportamentos bacterianos tais como a formação de biofilmes, virulência e produção de antibióticos.

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