Bioinorganic Chemistry and Peptide Design

The Bioinorganic Chemistry and Peptide Design Laboratory works on the design and synthesis of peptides and peptidomimetics capable of coordinating different metal ions and displaying different properties and functions.

Research Interests

The research in this new group lies in the field of inorganic chemistry as it interfaces with biological, catalytic and medicinal chemistry. We are particularly interested in designing peptides and peptidomimetics that contain binding sites with high specificity for metal ions. Following nature´s lead and taking benefit of the advances in synthetic chemistry, we are generating different types of well defined tridimensional structures that present attractive opportunities for the design of functional molecules. We are using these protein-like structures as starting frameworks to introduce metal binding sites, which either mimic the active center of natural metalloenzymes or are novel sites, and tailor the metal ion properties to achieve known and new functionalities. The fact that these peptides and peptidomimetics are produced by chemical synthesis opens the door to the introduction of unnatural amino acids and chemical probes in specific positions. In addition, one has the potential to coordinate any type of transition metal ions, expanding in this way the scope of functionalities that one can evolve.

Superoxide radicals are one of the most toxic reactive oxygen species and its damaging effects lead to a variety of detrimental health conditions including cardiovascular diseases, neurodegenerative disorders, and other types of age-related diseases. Inspired by the structure and function of natural superoxide dismutases, metalloenzymes that catalyze the disproportionation of superoxide radicals to molecular oxygen and hydrogen peroxide, we are currently developing metallopeptides for the removal of these toxic radicals. Our driven force is the need of better tools to test the role of these radicals in different biological processes and better therapeutics agents for oxidative stress related diseases.

Another important area in our group is the development of metallopeptide-based catalysts for asymmetric reduction and oxidation reactions. Recent years have seen a tremendous demand for efficient and environmentally friendly industrial processes to prepare enantiomerically pure compounds. This big challenge has become a powerful stimulus for the development of better and new catalysts. In this context, we are exploring the use of peptides and peptidomimetics to design a new generation of hybrid catalysts where the reactivity of a transition metal center will be combined with the chiral environment of the peptidic-based scaffold.
 

Group Members

• Dr. Kotha Laxma Reddy
• Ana Fragoso
• Henrique Carvalho
• Sílvia Leite

Selected Publications 

1. S. Pires, J. Habjanič, M. Sezer, C. M. Soares, L. Hemmingsen, O. Iranzo. “Design of a peptidic turn with high affinity for Hg(II)”. Inorg. Chem., 2012, 51, 11339−11348
2. O. Iranzo, T. Jakusch, K-H Lee, L. Hemmingsen and V. L. Pecoraro. “The Correlation of ¹¹³Cd NMR and ^111mCd PAC Spectroscopies Provides a Powerful Approach for the Characterization of the Structure of Cd(II)-Substituted Zn(II) Proteins”. Chem. Eur. J., 2009, 15, 3761-3772
3. O. Iranzo, C. Cabello and V. L. Pecoraro. “Heterochromia in Designed Metallopeptides: Geometry-Selective Binding of Cd(II) in a De Novo Peptide”. Angew. Chem. Int. Ed., 2007, 46, 6688-6691

Laboratory's Website

For further information please visit the laboratory's website

Química Bioinorgânica e Design de Péptidos (PT)

Em certas condições, o nosso corpo consegue produzir níveis elevados de radicais superoxidos, espécies tóxicas que em concentrações elevadas podem provocar doenças degenerativas cardíacas e neurológicas. Para nos proteger do efeito destas moléculas, o nosso corpo possui enzimas – superoxido dismutases – capazes de eliminar especificamente os radicais superoxidos. Há medicamentos que mimetizam a acção destas enzimas e que são hoje, em dia, administrados em caso de ataque cardíaco ou AVC. No entanto, as superoxido dismutase são muito mais eficazes na destruição dos radicais superoxidos do que estes compostos. A investigação no nosso laboratório tem como objectivo construir novas moléculas, que sejam semelhantes às enzimas, utilizando os mesmos blocos de construção (os aminoácidos) e os metais manganês e ferro. A investigação que fazemos pode ser o ponto de partida para o desenvolvimento de melhores fármacos antioxidantes e dá-nos também ferramentas para compreender melhor o papel dos radicais superoxidos no nosso corpo.

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