Solution- and solid-phase syntheses of guanidine-bridged, water-soluble linkers for multivalent ligand design.
[reaction: see text] Efficient syntheses of guanidine-bridged poly(ethylene glycol) linkers of various lengths in fully protected form are reported for both solution- and solid-phase protocols. The application of such linkers in the construction of water-soluble and high-affinity multivalent ligands against cholera toxin is demonstrated. Synthetic intermediates for multivalent ligands as large as 20 kDa in molecular weight have been assembled using presynthesized linkers. The final ligands are highly water-soluble, thus enabling proper biophysical characterization.
Zhang
Zhongsheng
Z
Biomolecular Structure Center, Department of Biochemistry, Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA.
Pickens
Jason C
JC
Hol
Wim G J
WG
Fan
Erkang
E
D002240:Carbohydrate Sequence; D002772:Cholera Toxin / Q000037:antagonists & inhibitors / Q000737:chemistry; D006146:Guanidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008024:Ligands; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012996:Solutions / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
D006146:Guanidines; D008024:Ligands; D012996:Solutions; D014867:Water; D011092:Polyethylene Glycols; D002772:Cholera Toxin