Intramolecular VersusIntermolecular Disulfide Bonds in Prion Proteins

Intramolecular versus intermolecular disulfide bonds in prion proteins.

Prion protein (PrP) is the major component of the partially protease-resistant aggregate that accumulates in mammals with transmissible spongiform encephalopathies. The two cysteines of the scrapie form, PrP(Sc), were found to be in their oxidized (i.e. disulfide) form (Turk, E., Teplow, D. B., Hood, L. E., and Prusiner, S. B. (1988) Eur. J. Biochem. 176, 21-30); however, uncertainty remains as...

A role for intermolecular disulfide bonds in prion diseases?

The key event in prion diseases seems to be the conversion of the prion protein PrP from its normal cellular isoform (PrP(C)) to an aberrant "scrapie" isoform (PrP(Sc)). Earlier studies have detected no covalent modification in the scrapie isoform and have concluded that the PrP(C) --> PrP(Sc) conversion is a purely conformational transition involving no chemical reactions. However, a reexamina...

Site-specific PEGylation of native disulfide bonds in therapeutic proteins.

Native disulfide bonds in therapeutic proteins are crucial for tertiary structure and biological activity and are therefore considered unsuitable for chemical modification. We show that native disulfides in human interferon alpha-2b and in a fragment of an antibody to CD4(+) can be modified by site-specific bisalkylation of the two cysteine sulfur atoms to form a three-carbon PEGylated bridge. ...

Formation of disulfide bonds in synthetic peptides and proteins.

A Reagent for Reduction of Disulfide Bonds in Proteins That Reduces Disulfide Bonds Faster Than Does Dithiothreitol

We have synthesized a new reagent-N,N'-dimethyl-N,.,V.bis(mercaptoacetyl)hydrazine(DMH)-for the reduction of disulfide bonds in proieins. DMH reduce.s disulfide bonds ? times faster than does dithiothreitol (DTT) in water at pH ?. DMH reduces mixed disulfides of cvsteine proteases (papain and ficin) especially rapdily i30 ti-.r faster than DTT). DMH (eo = -0.300 V) reduces noncl'clic disulfides...