Research Article

N-glycosylation of enhanced aromatic sequons to increase glycoprotein stability†

  1. Joshua L. Price1,
  2. Elizabeth K. Culyba2,3,
  3. Wentao Chen2,3,
  4. Amber N. Murray2,3,
  5. Sarah R. Hanson2,3,
  6. Chi-Huey Wong2,3,
  7. Evan T. Powers2,3,*,
  8. Jeffery W. Kelly2,3,4,*

Article first published online: 3 FEB 2012

DOI: 10.1002/bip.22030

Issue

Peptide Science

Peptide Science

Volume 98, Issue 3, pages 195–211, 2012

Additional Information

How to Cite

Price, J. L., Culyba, E. K., Chen, W., Murray, A. N., Hanson, S. R., Wong, C.-H., Powers, E. T. and Kelly, J. W. (2012), N-glycosylation of enhanced aromatic sequons to increase glycoprotein stability. Biopolymers, 98: 195–211. doi: 10.1002/bip.22030

Author Information

  1. 1

    Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602

  2. 2

    Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037

  3. 3

    The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037

  4. 4

    Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037

*Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, USA

  1. †

    This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers©wiley.com

Publication History

  1. Issue published online: 14 MAY 2012
  2. Article first published online: 3 FEB 2012
  3. Manuscript Accepted: 26 JAN 2012
  4. Manuscript Revised: 17 JAN 2012
  5. Manuscript Received: 18 OCT 2011

Funded by

  • Skaggs Institute for Chemical Biology, The Lita Annenberg Hazen Foundation
  • National Institutes of Health (NIH). Grant Numbers: GM051105, AI072155
  • NIH Post-Doctoral Fellowship. Grant Number: F32 GM086039

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Keywords:

  • N-glycosylation;
  • enhanced aromatic sequons;
  • glycoproteins

Abstract

N-glycosylation can increase the rate of protein folding, enhance thermodynamic stability, and slow protein unfolding; however, the molecular basis for these effects is incompletely understood. Without clear engineering guidelines, attempts to use N-glycosylation as an approach for stabilizing proteins have resulted in unpredictable energetic consequences. Here, we review the recent development of three “enhanced aromatic sequons,” which appear to facilitate stabilizing native-state interactions between Phe, Asn-GlcNAc and Thr when placed in an appropriate reverse turn context. It has proven to be straightforward to engineer a stabilizing enhanced aromatic sequon into glycosylation-naïve proteins that have not evolved to optimize specific protein–carbohydrate interactions. Incorporating these enhanced aromatic sequons into appropriate reverse turn types within proteins should enhance the well-known pharmacokinetic benefits of N-glycosylation-based stabilization by lowering the population of protease-susceptible unfolded and aggregation-prone misfolded states, thereby making such proteins more useful in research and pharmaceutical applications. © 2011 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 98: 195–211, 2012.

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