Event Title

Monodisperse oligomeric hemoglobin for use in critical care

Research Mentor(s)

Spencer Anthony-Cahill

Description

Preclinical studies with polymerized hemoglobin (Hb) molecules of high molecular weight (MW) have been shown to decrease previously observed adverse side effects associated with the administration of cell-­‐free monomeric or low-­‐molecular weight hemoglobin solutions. Non-­‐specific chemical crosslinking methods are used to create these high MW Hb polymers, leading to a heterogeneous product mixture. We propose to develop a method to generate higher MW Hbs (i.e. covalent linkage of > 4 Hb molecules) based on click chemistry between an azide-­‐derivatized dendrimer scaffold and Hbs that have been modified with a strained cyclooctyne. The derivatized dedrimers can be purchased and the modified Hb can be generated using the site specific ligation reaction of the sortase A enzyme from S. aureus. Current work in our lab has established that sortase A can be used to derivatize Hb with fluorescent tags and a dibenzocyclooctyne (DBCO). Initial attempts to react the azide dendrimer with the DBCO-­‐modified Hb have just been initiated in our lab. The work proposed for this project will focus on optimization of the click chemistry and characterization of the polymeric product(s).

Document Type

Event

Start Date

May 2018

End Date

May 2018

Location

Chemistry

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

This document is currently not available here.

Share

COinS
 
May 16th, 12:00 PM May 16th, 3:00 PM

Monodisperse oligomeric hemoglobin for use in critical care

Chemistry

Preclinical studies with polymerized hemoglobin (Hb) molecules of high molecular weight (MW) have been shown to decrease previously observed adverse side effects associated with the administration of cell-­‐free monomeric or low-­‐molecular weight hemoglobin solutions. Non-­‐specific chemical crosslinking methods are used to create these high MW Hb polymers, leading to a heterogeneous product mixture. We propose to develop a method to generate higher MW Hbs (i.e. covalent linkage of > 4 Hb molecules) based on click chemistry between an azide-­‐derivatized dendrimer scaffold and Hbs that have been modified with a strained cyclooctyne. The derivatized dedrimers can be purchased and the modified Hb can be generated using the site specific ligation reaction of the sortase A enzyme from S. aureus. Current work in our lab has established that sortase A can be used to derivatize Hb with fluorescent tags and a dibenzocyclooctyne (DBCO). Initial attempts to react the azide dendrimer with the DBCO-­‐modified Hb have just been initiated in our lab. The work proposed for this project will focus on optimization of the click chemistry and characterization of the polymeric product(s).