Chemistry and Molecular PharmacologyCombinatorial chemistry for the discovery of new compounds

Combinatorial chemistry for the discovery of new compounds

Fernando Albericio

Group Leader

Professor (Organic Chemistry Dept. - UB)

+34 93 40 37088

This group applies sciences to obtain two types of new compounds: pharmacological agents (medicinal chemistry) and polymers (new materials field). Our research involves two complementary elements: the exploration of new methodologies for the preparation of libraries, and the application of these methodologies in the search for new compounds. In terms of methodology, we work on supports, handles, scaffolds and privileged structures that interact with two or more unrelated receptors. In the field of medicinal chemistry, our studies focus mainly on two types of processes: cancer and disorders of the central nervous system.

a) Synthesis and structural assignation of peptides with bioactivity

Marine Peptides. In this sub-project, we focus on structurally different compounds: kahalalide F (currently in Phase III clinical trials), cyclopeptides, and peptides with concatenated azols. Our main interests are: the analogingof natural compounds to increase the potency of natural compounds such as kahalalide F; the preparation of analog libraries to improve ADME properties; and the development of synthetic methodologies for these compounds.

Peptidic Cancer Vaccines: This project addresses the rational development of synthetic, peptide-based vaccines for the treatment of melanoma. To eliminate tumours and prevent their proliferation to other organs (metastasis), a cancer vaccine must have the capacity to selectively induce both cellular (cytotoxic T cells) and humoral (specific B lymphocytes) immune responses. The structural flexibility of the peptidic vaccines proposed would facilitate the development of cancer-specific and patient-specific therapeutic strategies. Furthermore, multiple antigens could be used on the same vaccine to increase its coverage and prevent the emergence of resistant variants.

b) Synthesis of polyheterocyclic nitrogen-containing systems

Marine invertebrates, such as sponges, tunicates, ascidians and corals, have provided a rich arsenal of new bioactive compounds. These compounds are characterized by unprecedented structures and are highly active against various tumour cell lines. We have synthesized several marine alkaloids (listed below) in solution or in solid-phase, and we are currently preparing libraries of related compounds and also developing total syntheses of new marine alkaloids. E.g.: Ascididemine, Variolin-B, Pyrrole Lamellarin derivatives, Pentacyclic Lamellarins

c) Solid-phase synthesis of bioactive libraries compounds

We use combinatorial chemistry to prepare medium-sized libraries, with a focus on improving the activity, physical properties or other characteristics of bioactive compounds.

d) New resins and linkers Solid-phase synthesis requires properly functionalized resins and linkers.

The resins can be used not only as supporting material for anchoring the scaffold and growing the compound but also as protecting group of a functionality of the reactive starting material. Our research in this field includes the modification of commercially available resins and the synthesis of new linkers.

e) The hexafluoroacetone chemistry (HFA)

The bi-functional application of HFA as protecting group and activating agent for a-hydroxyacids is useful for the preparation of depsipeptides and other compounds of biological interest. We are currently preparing depsipeptidic analogs of Cilengitide (Merck) and also libraries of peptides and glycosidic compounds.

Torres A, Mas-Moruno C, Pérez-Payá E, Albericio F, Royo M.
Bioconjugate Chem (22), 2172-2178 (2011)

People

Upcoming events

29 Oct

Speaker: Dr. James Gordon,
Structural Characterization of macromolecular assemblies, IRB Barcelona, Spain

29 Oct

Speaker: Dr. Maribel Geli,
The endocytic pathway and the actin cytoskeleton, IBMB- CSIC, Barcelona, Spain

31 Oct

Speaker: Dr. Alfonso Martínez Arias,
Dept. of Genetics, University of Cambridge, UK

Funding

This group receives financial support from the following sources:

  • Comisión Interministerial de Ciencia y Tecnología (Interministerial Commission for Science and Technology)
  • Fundació La Marató de TV3 ("La Marató de TV3" Foundation)
  • Secretaría de Estado de Cooperación Internacional (AECI)(Spanish Agency for International Cooperation)