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Conformational Isomers of Denatured and Unfolded Proteins: Methods of Production and Applications

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Abstract

Conformational isomers of denatured-unfolded proteins are rich in numbers and varied in shapes. They represent an opulent resource of biological molecules that have remained unexploited. The major obstacle in utilizing this untapped potential is that it is inherently difficult to isolate and characterize pure conformational isomers, not only because of the excessive large number, but also because of their instability and rapid inter-conversion. Our lab has developed a method for trapping selected conformational isomers of denatured proteins that are amenable to isolation, characterization and further applications. The method has potential usefulness, ranging from the comprehensive structural characterization of denatured proteins, to the elucidation of pathways of protein unfolding–folding, to the production of unlimited structurally defined non-native protein isomers for biomedical applications.

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Abbreviations

α-LA:

α-Lactalbumin

HPLC:

High pressure liquid chromatography

MALDI-TOF:

Matrix assisted laser desorption ionization/time-of flight

BPTI:

Bovine pancreatic trypsin inhibitor

TAP:

Tick anticoagulant peptide

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Acknowledgments

The authors wish to acknowledge the support of IsoVax Therapeutic Inc. and the endowment from the Robert Welch foundation. Both JYC and The University of Texas are share holders of IsoVax Therapeutic Inc. The author also thanks Dr. M. S. Sy for carrying out immunogenicity studies of X-α-LA.

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Authors and Affiliations

  1. Research Center for Protein Chemistry, Brown Foundation Institute of Molecular Medicine, The University of Texas, 1825 Pressler Street, Houston, TX, 77030, USA

    Jui-Yoa Chang

  2. The Department of Biochemistry and Molecular Biology, The University of Texas, 1825 Pressler Street, Houston, TX, 77030, USA

    Jui-Yoa Chang

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Correspondence to Jui-Yoa Chang.

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Chang, JY. Conformational Isomers of Denatured and Unfolded Proteins: Methods of Production and Applications. Protein J 28, 44–56 (2009). https://doi.org/10.1007/s10930-009-9162-7

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