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Biomedical subjects

Ricardo L E Furlan

Publications and source records attributed to Ricardo L E Furlan.

8 recordsLinked to original sources
PubMed2006

Chemically engineered extracts as an alternative source of bioactive natural product-like compounds.

The access to libraries of molecules with interesting biomolecular properties is a limiting step in the drug discovery process. By virtue of a long molecular evolution process, natural products are recognized as biologically validated starting points in structural space for library development. We introduce here a strategy to generate natural product-like libraries. A semisynthetic mixture of compounds was produced by diversification of a natural product extract through the chemical transformation of common chemical functionalities in natural products into chemical functionalities rarely found in nature. The resulting mixture showed antifungal activity against Candida albicans, whereas the starting extract did not show such activity. Bioguided fractionation led to the isolation of a previously undescribed active semisynthetic pyrazole. The result illustrates how biological activity can be generated by designed chemical diversification of a natural product mixture, and represents the proof of principle of an alternative strategy for producing natural product-like libraries from natural products libraries.

Antifungal Agents↗
PubMed2003

Metal-ion induced amplification of three receptors from dynamic combinatorial libraries of peptide-hydrazones.

Three building blocks of general structure (MeO)2 CH-aromatic linker-Pro-amino acid-NHNH2 have been prepared and tested in acid-catalysed dynamic combinatorial libraries. Exposure of these libraries to LiI and NaI led to the amplification of three macrocyclic pseudopeptide receptors. The receptors were isolated and their interactions with LiI and NaI were analysed using NMR, IR and ITC. Binding of the metal ions to the receptors is invariably entropy-driven. Nevertheless, all receptors were found to be flexible with substantial conformational rearrangements accompanying guest binding. This type of receptor is extremely difficult to access through rational design and the fact that dynamic combinatorial chemistry allows facile access to these challenging molecules underlines the power of the dynamic approach.

Combinatorial Chemistry Techniques↗
PubMed2002

Selection and amplification of hosts from dynamic combinatorial libraries of macrocyclic disulfides.

We have discovered two receptors for two different guests from a single dynamic combinatorial library. Each of the two guests amplifies the formation of a tightly binding host at the expense of unfit library members. Small differences in host-guest binding translate into useful differences in amplification. The selected hosts could be readily synthesized using biased dynamic libraries that contain only the right ratio of those building blocks that were selected by the guests. These results establish dynamic combinatorial chemistry as a practical method not only for the discovery but also for the synthesis of new receptors.

Journal Article↗
PubMed2002

Dynamic combinatorial chemistry.

A combinatorial library that responds to its target by increasing the concentration of strong binders at the expense of weak binders sounds ideal. Dynamic combinatorial chemistry has the potential to achieve exactly this. In this review, we will highlight the unique features that distinguish dynamic combinatorial chemistry from traditional combinatorial chemistry, and that could make a useful addition to the set of combinatorial techniques used in drug discovery.

Combinatorial Chemistry Techniques↗
PubMed2002

Recent developments in dynamic combinatorial chemistry.

Generating combinatorial libraries under equilibrium conditions has the important advantage that the libraries are adaptive (i.e. they can respond to exterior influences in the form of molecular recognition events). Thus, a ligand will direct and amplify the formation of its ideal receptor and vice versa. Proof of principle of this approach has been established using small libraries showing highly efficient amplification of selected receptors. The approach has recently been extended to address folding of macromolecules, including peptides.

Combinatorial Chemistry Techniques↗
PubMedDate not supplied

A rapid TLC autographic method for the detection of xanthine oxidase inhibitors and superoxide scavengers.

A new bioautographic assay suitable for the localization of xanthine oxidase inhibitors and superoxide radical scavengers present in a complex matrix is described. Enzyme activity is detected by reaction of superoxide radicals with nitroblue tetrazolium to form a blue formazan salt. Both activities can be differentiated using a non-enzymatic version of the autographic assay wherein superoxide is chemically generated.

Chromatography, Thin Layer↗