Multivalent scaffolds for affinity maturation of small molecule cell surface binders and their application to prostate tumor targeting.

Valerie Humblet, Preeti Misra, Kumar R. Bhushan, Khaled Nasr, Yao Sen Ko, Takashi Tsukamoto, Nadine Pannier, John V. Frangioni, Wolfgang Maison

Research output: Contribution to journalArticlepeer-review

Abstract

Adamantane scaffolds for affinity maturation of prostate cancer specific ligands of low molecular mass are described. These scaffolds are modular and can be used for conjugation of up to three ligands and an additional effector molecule by standard peptide coupling techniques. The potential of the scaffolds is demonstrated with the multimerization of GPI 1, a prostate cancer specific small molecule. A detailed study of multimerized GPI conjugates with near-infrared fluorophores and their binding properties to different prostate cancer cell lines shows the specific binding of these conjugates to cell types positive for prostate specific membrane antigen (PSMA). We demonstrate that these conjugates allow the sensitive imaging of prostate cancer cells with NIR methodology and suggest that our adamantane scaffolds might be generally useful for affinity maturation of small molecules targeting cell surface epitopes.

Original languageEnglish (US)
Pages (from-to)544-550
Number of pages7
JournalJournal of medicinal chemistry
Volume52
Issue number2
DOIs
StatePublished - Jan 22 2009
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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