Exploiting the Reactivity of Sortase Homologs for Generating Isopeptide Bonds
Research Mentor(s)
Antos, John M.
Description
Chemically modified proteins are critical components of modern therapeutics and basic research. In order to access these materials, precise and reproducible methods for the manipulation of protein structure and properties are required. With this need in mind, sortase enzymes have risen to prominence due to their ability to catalyze highly selective ligations between protein targets and useful functional groups not typically encountered in nature. To expand on these capabilities, we are working to exploit the reactivity of sortase homologs for generating isopeptide bonds. Sortase analogs from S. suis were found to preferentially form isopeptide linkages in vitro, as confirmed by LC-MS and HPLC analysis. Optimization of model reactions will be presented as well as progress toward determining the optimal structure of suitable lysine-containing reaction components. Additionally, we will be discussing recent work using Ni(II) coordination to sequester reaction by-products and to push the reaction equilibrium towards products.
Document Type
Event
Start Date
16-5-2018 9:00 AM
End Date
16-5-2018 12:00 PM
Department
Chemistry
Genre/Form
student projects, posters
Subjects – Topical (LCSH)
Proteins--Structure; Proteins--Biotechnology; Genetic engineering
Type
Image
Rights
Copying of this document in whole or in part is allowable only for scholarly purposes. It is understood, however, that any copying or publication of this document for commercial purposes, or for financial gain, shall not be allowed without the author’s written permission.
Language
English
Format
application/pdf
Exploiting the Reactivity of Sortase Homologs for Generating Isopeptide Bonds
Chemically modified proteins are critical components of modern therapeutics and basic research. In order to access these materials, precise and reproducible methods for the manipulation of protein structure and properties are required. With this need in mind, sortase enzymes have risen to prominence due to their ability to catalyze highly selective ligations between protein targets and useful functional groups not typically encountered in nature. To expand on these capabilities, we are working to exploit the reactivity of sortase homologs for generating isopeptide bonds. Sortase analogs from S. suis were found to preferentially form isopeptide linkages in vitro, as confirmed by LC-MS and HPLC analysis. Optimization of model reactions will be presented as well as progress toward determining the optimal structure of suitable lysine-containing reaction components. Additionally, we will be discussing recent work using Ni(II) coordination to sequester reaction by-products and to push the reaction equilibrium towards products.
Comments
Outstanding Poster Award Recipient