N-PEGylation of a reverse turn is stabilizing in multiple sequence contexts, unlike N-GlcNAcylation.

ABSTRACT: The intrinsic stabilization of therapeutic proteins by N-glycosylation can endow them with increased shelf and serum half-lives owing to lower populations of misfolded and unfolded states, which are susceptible to aggregation and proteolysis. Conjugation of poly(ethylene glycol) (PEG) oligomers to nucleophilic groups on the surfaces of folded proteins (i.e., PEGylation) is a chemical alternative to N-glycosylation, in that it can also enhance the pharmacologic attributes of therapeutic proteins. However, the energetic consequences of PEGylation are currently not predictable. We find that PEGylation of an Asn residue in reverse turn 1 of the Pin WW domain is intrinsically stabilizing in several sequence contexts, unlike N-glycosylation, which is only stabilizing in a particular sequence con

SUBMITTER: Price JL 

PROVIDER: S-EPMC3220771 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature