Gold nanoparticles decorated with mannose-6-phosphate analogues

Molecules. 2014 Jan 17;19(1):1120-49. doi: 10.3390/molecules19011120.

Abstract

Herein, the preparation of neoglycoconjugates bearing mannose-6-phosphate analogues is described by: (a) synthesis of a cyclic sulfate precursor to access the carbohydrate head-group by nucleophilic displacement with an appropriate nucleophile; (b) introduction of spacers on the mannose-6-phosphate analogues via Huisgen's cycloaddition, the Julia reaction, or the thiol-ene reaction under ultrasound activation. With the resulting compounds in hand, gold nanoparticles could be functionalized with various carbohydrate derivatives (glycoconjugates) and then tested for angiogenic activity. It was observed that the length and flexibility of the spacer separating the sugar analogue from the nanoparticle have little influence on the biological response. One particular nanoparticle system substantially inhibits blood vessel growth in contrast to activation by the corresponding monomeric glycoconjugate, thereby demonstrating the importance of multivalency in angiogenic activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inducing Agents / chemical synthesis*
  • Angiogenesis Inducing Agents / pharmacology
  • Animals
  • Chick Embryo
  • Chorioallantoic Membrane / blood supply
  • Click Chemistry
  • Cycloaddition Reaction
  • Gold / chemistry*
  • Halogenation
  • Mannosephosphates / chemistry*
  • Metal Nanoparticles / chemistry*
  • Neovascularization, Physiologic / drug effects
  • Particle Size

Substances

  • Angiogenesis Inducing Agents
  • Mannosephosphates
  • mannose-6-phosphate
  • Gold