The early career academics presenting in the next Peptide and Protein Science online series will be Marina Rubini from the University of University College Dublin and Drew Thompson from the University of Glasgow.
Date: 07-10-2022
Time: 1:00-2:00 pm
Venue: an online Zoom lecture
Registration: https://eu01web.zoom.us/meeting/register/u5EtdO6pqD8tG9xdGTIjCs9XgMel0RmutBIa
Drew Thomson 鈥� University of Glasgow
Title: Design and Synthesis of Protein Binding Modules
Abstract: Small protein domains mediate an array of vital biological processes, and frequently act as recognition domains to mediate protein-protein interactions in cell signalling processes. Our goal is to produce minimal versions of these protein domains as a means of binding their cognate partners in order to generate tool compounds for chemical biology. To do this we use a mix of peptide chemistry and chemical ligation methods, guided by computational design tools. Recent work in our group has, for example, targeted minimal binders of ubiquitin. To achieve this we have patterned residues from a known ubiquitin binding protein onto a chemically-crosslinked, designed dimeric alpha-helical coiled coil peptide. Despite its comparatively small size, this structure is stably folded, and displays a binding surface that closely mimics that of the original protein. Preliminary binding studies show that this peptide binds ubiquitin with a high (sub-micromolar) affinity. Current work is aimed at tuning this affinity, as well as engineering selectivity between different ubiqiuitin-like domains. Our eventual goal for this project is to produce multivalent binders that are capable of selectively sensing different polyubiquitin chain lengths and linkage topologies.
Marina Rubini 鈥� University College Dublin (link to profile)
Title: Non-natural amino acids and bio-orthogonal ligations in protein engineering
Abstract: We use semisynthetic approaches for engineering therapeutic proteins by means of non-natural amino acids to study the effect of post-translational modifications, such as glycosylations, at a molecular level. Moreover, we use glycan replacements by other hydrophilic polymer chains such as PEG to distinguish between sugar-specific or solubility-based effects. The introduced non-natural amino acids provide orthogonal sites for the chemo-selective conjugation of carbohydrate or PEG moieties by different ligation methods. Further, we used fluorinated amino acids for getting new insight into protein folding pathways and for modulating the biological properties of antifungal lipopeptides, such as Iturin A.
For upcoming series, please visit the RSC PPSG website (hyperlink).
If you would like to present in future seminars, please contact one of the organisers.
Louis Luk: lukly@cardiff.ac.uk
Chris Coxon: chris.coxon@ed.ac.uk
Louise Walport: louise.walport@crick.ac.uk
Date: 07-10-2022
Time: 1:00-2:00 pm
Venue: an online Zoom lecture
Registration: https://eu01web.zoom.us/meeting/register/u5EtdO6pqD8tG9xdGTIjCs9XgMel0RmutBIa
Drew Thomson 鈥� University of Glasgow
Title: Design and Synthesis of Protein Binding Modules
Abstract: Small protein domains mediate an array of vital biological processes, and frequently act as recognition domains to mediate protein-protein interactions in cell signalling processes. Our goal is to produce minimal versions of these protein domains as a means of binding their cognate partners in order to generate tool compounds for chemical biology. To do this we use a mix of peptide chemistry and chemical ligation methods, guided by computational design tools. Recent work in our group has, for example, targeted minimal binders of ubiquitin. To achieve this we have patterned residues from a known ubiquitin binding protein onto a chemically-crosslinked, designed dimeric alpha-helical coiled coil peptide. Despite its comparatively small size, this structure is stably folded, and displays a binding surface that closely mimics that of the original protein. Preliminary binding studies show that this peptide binds ubiquitin with a high (sub-micromolar) affinity. Current work is aimed at tuning this affinity, as well as engineering selectivity between different ubiqiuitin-like domains. Our eventual goal for this project is to produce multivalent binders that are capable of selectively sensing different polyubiquitin chain lengths and linkage topologies.
Marina Rubini 鈥� University College Dublin (link to profile)
Title: Non-natural amino acids and bio-orthogonal ligations in protein engineering
Abstract: We use semisynthetic approaches for engineering therapeutic proteins by means of non-natural amino acids to study the effect of post-translational modifications, such as glycosylations, at a molecular level. Moreover, we use glycan replacements by other hydrophilic polymer chains such as PEG to distinguish between sugar-specific or solubility-based effects. The introduced non-natural amino acids provide orthogonal sites for the chemo-selective conjugation of carbohydrate or PEG moieties by different ligation methods. Further, we used fluorinated amino acids for getting new insight into protein folding pathways and for modulating the biological properties of antifungal lipopeptides, such as Iturin A.
For upcoming series, please visit the RSC PPSG website (hyperlink).
If you would like to present in future seminars, please contact one of the organisers.
Louis Luk: lukly@cardiff.ac.uk
Chris Coxon: chris.coxon@ed.ac.uk
Louise Walport: louise.walport@crick.ac.uk
