Designed Proteins as Optimized Oxygen Carriers for Artificial Blood

Abstract

This project concerns the transformation of a de novo designed oxygen transport protein into an effective blood substitute. The protein is less than one-third the size of the human hemoglobin monomer, binds two as opposed to one oxygen-carrying heme cofactor per monomer, and is much more temperature stable than human hemoglobin (1). Therefore the protein promises to have a much higher oxygen capacity per unit weight and per unit volume than human hemoglobin. The stepwise goals of the project are to (A) extend the oxyferrous state lifetime by raising the cofactor reduction potential, (B) to optimize the molecular oxygen binding constant to that of human hemoglobin and (C) to create a crosslinked, stabilized preparation of the optimized protein. In the first two years of the project, Aim B was completed and some progress was made on Aim A, the most difficult Aim. Below we describe year three progress, which includes major advances in Aim A, progress in Aim C, and the additional engineering of a new enzymatic activity which addresses a major problem which has been raised in the literature subsequent to the start of the project.

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Document Details

Document Type
Technical Report
Publication Date
Feb 01, 2014
Accession Number
ADA622324

Entities

People

  • Ronald L. Koder

Organizations

  • City College of New York

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Biomedical And Dental Materials
  • Blood
  • Blood Substitutes
  • Cardiovascular System
  • Carrier Proteins
  • Chemical Synthesis
  • Chemistry
  • Engineering
  • Hemoglobin
  • New York
  • Proteins
  • Resonance
  • Spectra
  • Three Dimensional
  • Transport Ships

Readers

  • Molecular and Cellular Biochemistry
  • Systems Analysis and Design