Monodisperse oligomeric hemoglobin for use in critical care
Research Mentor(s)
Anthony-Cahill, Spencer J.
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
16-5-2018 12:00 AM
End Date
16-5-2018 12:00 AM
Department
Chemistry
Genre/Form
student projects, posters
Subjects – Topical (LCSH)
Hemoglobin; Biomedical 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
Monodisperse oligomeric hemoglobin for use in critical care
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).