Synthesis and Binding Studies of Alzheimer Ligands on Solid Support

Petra Rzepecki, Nina Geib, Manuel Peifer, Frank Biesemeier, and Thomas Schrader*
Fachbereich Chemie, Universitt Marburg, Hans-Meerwein-Strasse, 35032 Marburg, Germany
J. Org. Chem., 2007, 72 (10), pp 3614–3624
DOI: 10.1021/jo061918x
Publication Date (Web): April 12, 2007
Copyright © 2007 American Chemical Society
*

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

, schradet@staff.uni-marburg.de

Abstract

Abstract Image

Aminopyrazole derivatives constitute the first class of nonpeptidic rationally designed β-sheet ligands. Here we describe a double solid-phase protocol for both synthesis and affinity testing. The presented solid-phase synthesis of four types of hybrid compounds relies on the Fmoc strategy and circumvents subsequent HPLC purification by precipitating the final product from organic solution in pure form. Hexa- and octapeptide pendants with internal di- and tetrapeptide bridges are now amenable in high yields to combinatorial synthesis of compound libraries for high-throughput screening purposes. Solid-phase peptide synthesis (SPPS) on an acid-resistant PAM allows us, after PMB deprotection, to subject the free aminopyrazole binding sites in an immobilized state to on-bead assays with fluorescence-labeled peptides. From the fluorescence emission intensity decrease, individual binding constants can be calculated via reference curves by simple application of the law of mass action. Gratifyingly, host/guest complexation can be monitored quantitatively even for those ligands, which are almost insoluble in water.

View: Full Text HTML | Hi-Res PDF

Tools

History

  • Published In Issue May 11, 2007
  • Received September 18, 2006

Recommend & Share

Related Content

Other ACS content by these authors: