Presentation Title

Functionalizing of Well-defined Poly-acrylates with TEMPO and PEG moieties for the Modification of Hemoglobin-Based Oxygen Carriers for the Treatment of Traumatic Brain Injuries

Location

Nessmith-Lane Atrium

Session Format

Poster Presentation

Research Area Topic:

Natural & Physical Sciences - Chemistry

Abstract

Hemoglobin, the main constituent of the red blood cell, carries and delivers oxygen throughout the body via the four heme subunits of the protein. Each heme group contains a central iron ion that readily binds with oxygen for transport. Injuries that result in significant blood loss, such as traumatic brain injuries (TBI), thus impede the cardiovascular system‰Ûªs ability to oxygenate the tissues, posing serious health concerns. The development of Hemoglobin-Based Oxygen Carriers (HBOCs) though holds promise as a treatment for such injuries by exploiting the oxygen transport mechanisms of cell-free hemoglobin to restore oxygen flow throughout the body. Utilizing cell-free hemoglobin eliminates the immunogenic complications associated with blood transfusions and also allows for the hemoglobin molecules to infiltrate swollen brain tissue. However, lacking the homeostatic control mechanisms of the red blood cell, these HBOCs have been found to scavenge nitric oxide and oversupply oxygen in arterioles, inflating blood pressure and causing oxidative damage. The latest generation of HBOCs, Polynitroxyl Pegylated Hemoglobin (PNPH), are attached with 2,2,6,6-tetramethylpiperidine-1-oxidyl (TEMPO), polyethylene glycol (PEG), and a cysteine-binding group (maleimiide). These functional groups reduce the oxidative effects and mediate the oxygen delivery of the hemoglobin. While treatment using PNPH has been approved by the Federal Drug Administration for clinical trials, the current synthesis involves a costly multistep procedure not conducive for large scale manufacturing of the treatment. This current research aims to develop a new synthetic strategy of acrylate polymers that reduces synthesis steps of PNPH. Primarily, a more efficient and practical synthetic strategy will be developed by conjugating acrylate monomers with the functional groups (TEMPO, PEG and cysteine-binding group) to attach to the hemoglobin molecule. The synthetic strategy will be generated based on Reversible Addition-Fragmentation chain Transfer (RAFT) polymerization using the acrylate functional groups. This synthetic strategy will allow for the PNPH to be synthesized more efficiently and cost effectively for the treatment of TBI. The research‰Ûªs framework is planned to be completed within the timeframe of this thesis. will be analyzed by gel permeation chromatography (GPC) and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry to determine their respective average molecular weights and polydispersities.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Presentation Type and Release Option

Presentation (Open Access)

Start Date

4-16-2016 10:45 AM

End Date

4-16-2016 12:00 PM

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Apr 16th, 10:45 AM Apr 16th, 12:00 PM

Functionalizing of Well-defined Poly-acrylates with TEMPO and PEG moieties for the Modification of Hemoglobin-Based Oxygen Carriers for the Treatment of Traumatic Brain Injuries

Nessmith-Lane Atrium

Hemoglobin, the main constituent of the red blood cell, carries and delivers oxygen throughout the body via the four heme subunits of the protein. Each heme group contains a central iron ion that readily binds with oxygen for transport. Injuries that result in significant blood loss, such as traumatic brain injuries (TBI), thus impede the cardiovascular system‰Ûªs ability to oxygenate the tissues, posing serious health concerns. The development of Hemoglobin-Based Oxygen Carriers (HBOCs) though holds promise as a treatment for such injuries by exploiting the oxygen transport mechanisms of cell-free hemoglobin to restore oxygen flow throughout the body. Utilizing cell-free hemoglobin eliminates the immunogenic complications associated with blood transfusions and also allows for the hemoglobin molecules to infiltrate swollen brain tissue. However, lacking the homeostatic control mechanisms of the red blood cell, these HBOCs have been found to scavenge nitric oxide and oversupply oxygen in arterioles, inflating blood pressure and causing oxidative damage. The latest generation of HBOCs, Polynitroxyl Pegylated Hemoglobin (PNPH), are attached with 2,2,6,6-tetramethylpiperidine-1-oxidyl (TEMPO), polyethylene glycol (PEG), and a cysteine-binding group (maleimiide). These functional groups reduce the oxidative effects and mediate the oxygen delivery of the hemoglobin. While treatment using PNPH has been approved by the Federal Drug Administration for clinical trials, the current synthesis involves a costly multistep procedure not conducive for large scale manufacturing of the treatment. This current research aims to develop a new synthetic strategy of acrylate polymers that reduces synthesis steps of PNPH. Primarily, a more efficient and practical synthetic strategy will be developed by conjugating acrylate monomers with the functional groups (TEMPO, PEG and cysteine-binding group) to attach to the hemoglobin molecule. The synthetic strategy will be generated based on Reversible Addition-Fragmentation chain Transfer (RAFT) polymerization using the acrylate functional groups. This synthetic strategy will allow for the PNPH to be synthesized more efficiently and cost effectively for the treatment of TBI. The research‰Ûªs framework is planned to be completed within the timeframe of this thesis. will be analyzed by gel permeation chromatography (GPC) and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry to determine their respective average molecular weights and polydispersities.