The Department of Chemistry, School of Arts and Sciences, Amrita Vishwa Vidyapeetham, Amritapuri campus, organized an invited talk on “Designed Peptide Platforms: from Concepts to Biotechnological Applications” on January 16, 2017. Dr. Olga Iranzo, Institute of Molecular Sciences of Marseille, Chargé de mission INC CNRS. Aix- Marseille Université France, was the resource person.
Topic: Designed Peptidic Platforms: from Concepts to Biotechnological Applications
Olga Iranzo, Aix-Marseille Université, CNRS, Centrale Marseille, iSm2, 13397 Marseille, France.
Abstract
The design of novel peptides/proteins with tailor-made properties and functionalities is a growing research discipline in the fields of chemistry, bioengineering and biomedicine. This is a multidisciplinary endeavor that requires the expertise of scientists from different areas. Chemists and bioengineers can play a critical role in this effort developing innovative computational and chemical strategies to produce robust scaffolds where one can have a precise control over the location of crucial elements, such as functional groups for target recognition or metal ion binding. These structures can therefore render new, cheaper and more stable alternatives for therapeutic, chemical, and biotechnological applications.
In this communication we will present two sets of peptidic scaffolds. On one hand, we have developed a family of bioinspired pre-organized small peptides capable of binding Cu(II) as catalysts for environmentally friendly chemical transformations. They contain multiple His and backbones with different degrees of conformational constrain. Spectroscopic and pH potentiometric data revealed the formation of similar major Cu(II) species at close to neutral pH value where Cu(II) is coordinated to the His. Nonetheless, due to the distinct flexible nature of their scaffolds different stability constants as well as Cu(II) exchange rates and redox potentials (Cu(II)/Cu(I)) were observed. All the complexes were able to oxidize sulfides in aqueous solution and at room temperature but different catalytic behaviours were observed reflecting their intrinsic properties. On the other hand, peptidic scaffolds based on WW domains were developed as affinity ligands for bioseparations in proteomics/phosphoproteomics. WW domains have been found in at least 200 multidomain proteins and are usually localized in the recognition region known to mediate protein-protein interactions.
Two WW domains were selected for our purpose: the Human Pin1 (hPin1_WW) that recognizes peptide ligands with Pro-rich sequences containing pSer/pThr-Pro, and the Human YAP65 (hYAP65_WW) that recognizes Pro-rich peptide sequences with Tyr. Small versions of both WW domains were chemically synthesized, immobilized in a solid support through Sulfo-SMCC chemistry, and tested for the affinity purification of their targets. The immobilized hPin1_WW domain was able to separate phosphorylated peptides/proteins and the solid support immobilized with the hYAP65_WW domain was employed in the purification of proline rich targets. In both cases, binding and elution were achieved using mild conditions.
Biography
Dr. Olga Iranzo obtained her doctorate in Chemistry at the University of Buffalo – SUNY in 2003 working on the design of artificial ribonucleases based on Zn(II) and Cu(II) complexes. In May 2004 she moved to the University of Michigan (Ann Arbor, USA) as a postdoctoral researcher to work on the field of De Novo designed metallopeptides. She developed three stranded coiled coil peptides capable of selectively binding different transition metal ions. Important insights into the characteristics of biological relevant metal ion binding sites were obtained that contributed to the understanding of how protein scaffolds attained their superb fine-tuning of metal ion properties. In 2008 she became the group leader of the Bioinorganic and Peptide Design group at the Instituto de Tecnologia Química e Biológica (Oeiras, Portugal). In 2013 she joined the Institut des Sciences Moléculaires de Marseille (UMR CNRS 7313 – Aix-Marseille Université) as CNRS CR1 researcher. Her research is focused in the design of bioinspired peptide-based platforms for biotechnological/biomedical applications as well as for the development of novel catalysts for environmentally friendly chemical transformations. Her interdisciplinary and highly collaborative research program involves chemical synthesis, bioinorganic chemistry, medicinal inorganic chemistry, biochemistry, biophysics, computational chemistry, and chemical engineering.