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. Second year accomplishments include: (A) The creation and verification of a theoretical model for oxyferrous state lifetimes in oxygen transport proteins. (B) We have modified global protein dynamics to double of oxyferrous state lifetime. (C) We have used surface side chain charges to increase the reduction potential of the bound cofactor and triple the oxyferrous state lifetime. (D) We have incorporated an optimized cofactor binding site and shown that the decrease in protein core dynamics increases the lifetime four-fold. (E) We have made significant progress on the determination of the three-dimensional structure of one of the best performing variants. After a limited amount of additional optimization, this protein is ready for incorporation into the crosslinked particles that are the goal of year three.

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Document Details

Document Type
Technical Report
Publication Date
Feb 01, 2013
Accession Number
ADA574241

Entities

People

  • Ronald L. Koder

Organizations

  • City College of New York

Tags

DTIC Thesaurus Topics

  • Biochemistry
  • Biomedical Research
  • Blood Substitutes
  • Carrier Proteins
  • Chemistry
  • Deuterium
  • Diseases And Disorders
  • Dynamics
  • Electric Fields
  • Hydrogen
  • Molecules
  • New York
  • Particles
  • Proteins
  • Raman Spectroscopy
  • Three Dimensional
  • Transport Ships

Readers

  • Molecular Photonics/Laser Physics
  • Molecular and Cellular Biochemistry