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N‐glycosylation of enhanced aromatic sequons to increase glycoprotein stability
Author(s) -
Price Joshua L.,
Culyba Elizabeth K.,
Chen Wentao,
Murray Amber N.,
Hanson Sarah R.,
Wong ChiHuey,
Powers Evan T.,
Kelly Jeffery W.
Publication year - 2012
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.22030
Subject(s) - chemistry , glycosylation , glycoprotein , biochemistry , biophysics , biology
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.