Using combinatorial methods to arrive at a quantitative structure-stability relationship for a new class of one-armed cationic peptide receptors targeting the C-terminus of the amyloid beta-peptide

Organic & Biomolecular Chemistry
Carsten Schmuck, Martin Heil

Abstract

A new class of one-armed tripeptide based cationic guanidiniocarbonyl pyrrole receptors is shown to strongly bind the tetrapeptide L-Val-L-Val-L-Ile-L-Ala, representing the C-terminus of the amyloid beta-peptide even under polar conditions. A medium sized combinatorial library of 125 receptors was synthesized on a solid support and their binding properties determined on bead using a quantitative fluorescence assay. The binding constants are in the order of 10(3)-10(4) M-1 (in the presence of a formate counter ion in methanol) for the most efficient ones but differ by more than a factor of 100 among the 125 library members. Based on the binding data of 12 receptors a structure-stability relationship was established for peptide binding by this new receptor class. Complex formation is controlled by a fine balanced interplay of hydrophobic and electrostatic interactions with none of these two interactions alone being strong enough to ensure complexation under these polar conditions.

Citations

Feb 19, 2005·Chembiochem : a European Journal of Chemical Biology·Carsten SchmuckMartin Heil
Nov 13, 2003·Chembiochem : a European Journal of Chemical Biology·Carsten Schmuck, Martin Heil
Apr 17, 2019·Angewandte Chemie·Guangzhu WangSenmiao Xu
May 16, 2020·ChemPlusChem·Michael GieseJens Voskuhl
Mar 13, 2012·Pharmacological Reviews·E J Verspohl
Jul 16, 2013·Nature Biotechnology·Soheil FeiziManolis Kellis
Jan 27, 2009·Chemical Society Reviews·Stefan Kubik

Related Concepts

Peptide Fragments
Plasma Protein Binding Capacity
Pyrroles
Structure-Activity Relationship
Amyloid beta-Peptides
Peptide Receptor
Molecular Mimicry
Synthetic Peptide Combinatorial Library
Combinatorial Chemistry Techniques

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