Details

Autor(en) / Beteiligte

• Zuckermann, Ronald N
• Martin, Eric J
• Spellmeyer, David C
• Stauber, Gregory B
• Shoemaker, Kevin R
• Kerr, Janice M
• Figliozzi, Gianine M
• Goff, Dane A
• Siani, Michael A
• Simon, Reyna J
• Banville, Steven C
• Brown, Edward G
• Wang, Liang
• Richter, Lutz S
• Moos, Walter H

Titel

Discovery of Nanomolar Ligands for 7-Transmembrane G-Protein-Coupled Receptors from a Diverse N-(Substituted)glycine Peptoid Library

Ist Teil von

• Journal of medicinal chemistry, 1994-08, Vol.37 (17), p.2678-2685

Ort / Verlag

Washington, DC: American Chemical Society

Erscheinungsjahr

1994

Quelle

MEDLINE

Beschreibungen/Notizen

• Screening a diverse, combinatorial library of ca. 5000 synthetic dimer and trimer N-(substituted)glycine "peptides" yielded novel, high-affinity ligands for 7-transmembrane G-protein-coupled receptors. The peptoid library was efficiently assembled using readily available chemical building blocks. The choice of side chains was biased to resemble known ligands to 7-transmembrane G-protein-coupled receptors. All peptides were screened in solution-phase, competitive radioligand-binding assays. Peptoid trimer CHIR 2279 binds to the alpha 1-adrenergic receptor with a Ki of 5 nM, and trimer CHIR 4531 binds to the mu-opiate receptor with a Ki of 6 nM. This represents the first example of the discovery of high-affinity receptor ligands from a combinatorial library of non-natural chemical entities.