NR AVRD
AU Marsac,Y.; Cramer,J.; Olschewski,D.; Alexandrov,K.; Becker,C.F.
TI Site-specific attachment of polyethylene glycol-like oligomers to proteins and peptides
QU Bioconjugate Chemistry 2006 Nov-Dec; 17(6): 1492-8
PT journal article; research support, non-u.s. gov't
AB Modification of proteins with polymers is a viable method to tune protein properties, e.g., to render them more water-soluble by using hydrophilic polymers. We have utilized precision-length, polyethylene glycol-based oligomers carrying a thioester moiety in transthioesterification and native chemical ligation reactions with internal and N-terminal cysteine residues in proteins and peptides. These reactions lead to uniquely modified proteins with an increased solubility in chaotrope- and detergent-free aqueous systems. Polymer modification of internal cysteines is fully reversible and allows generation of stable protein-polymer conjugates for enzymatic manipulations as demonstrated by proteolytic cleavage of a protein construct that was only soluble in buffers incompatible with protease activity before polymer modification. The permanent polymer modification of a Rab protein at its N-terminal cysteine produced a fully active Rab variant that was efficiently prenylated. Thus, PEGylation of prenylated proteins might be a viable route to increase water solubility of such proteins in order to carry out experiments in detergent- and lipid-free systems.
MH Molecular Structure; Peptides/*chemistry; Polyethylene Glycols/*chemistry; Prions/*chemistry/genetics/metabolism; Spectrometry, Mass, Electrospray Ionization; rab GTP-Binding Proteins/*chemistry
AD Max-Planck Institute of Molecular Physiology, Department of Physical Biochemistry, Otto-Hahn Str. 11, 44227 Dortmund, Germany.
SP englisch
PO USA