Multivalent peptidomimetic conjugates

A versatile platform for modulating androgen receptor activity

Paul M. Levine, Keren Imberg, Michael J. Garabedian, Kent Kirshenbaum

Research output: Contribution to journalArticle

Abstract

We introduce a family of multivalent peptidomimetic conjugates that modulate the activity of the androgen receptor (AR). Bioactive ethisterone ligands were conjugated to a set of sequence-specific peptoid oligomers. Certain multivalent peptoid conjugates enhance AR-mediated transcriptional activation. We identify a linear and a cyclic conjugate that exhibit potent anti-proliferative activity in LNCaP-abl cells, a model of therapy-resistant prostate cancer. The linear conjugate blocks AR action by competing for ligand binding. In contrast, the cyclic conjugate is active despite its inability to compete against endogenous ligand for binding to AR in vitro, suggesting a non-competitive mode of action. These results establish a versatile platform to design competitive and non-competitive AR modulators with potential therapeutic significance.

Original languageEnglish (US)
Pages (from-to)6912-6915
Number of pages4
JournalJournal of the American Chemical Society
Volume134
Issue number16
DOIs
StatePublished - Apr 25 2012

Fingerprint

Peptidomimetics
Androgen Receptors
Peptoids
Ligands
Ethisterone
Oligomers
Modulators
Transcriptional Activation
Prostatic Neoplasms
Chemical activation
Androgens
Therapeutics

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Multivalent peptidomimetic conjugates : A versatile platform for modulating androgen receptor activity. / Levine, Paul M.; Imberg, Keren; Garabedian, Michael J.; Kirshenbaum, Kent.

In: Journal of the American Chemical Society, Vol. 134, No. 16, 25.04.2012, p. 6912-6915.

Research output: Contribution to journalArticle

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