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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.

Carsten Schmuck·Martin Heil
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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.

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Amyloid beta-PeptidesBinding SitesCombinatorial Chemistry TechniquesHumansMolecular MimicryPeptide FragmentsPeptide LibraryProtein BindingPyrrolesReceptors, PeptideStructure-Activity RelationshipJournal ArticleResearch Support, Non-U.S. Gov't

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Carsten Schmuck, Martin Heil. 2003-02-21. 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.. https://doi.org/10.1039/b211425a

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