Use of self-assembled monolayers to probe the structure of a target molecule

Abstract

Weak binding motifs were transformed into a high affinity ligand surface by using a heterologous self-assembled monolayer (SAM) as a rigid scaffold to present discrete binding moieties, in a controlled geometry, to a target molecule. At a critical ligand density, the discrete binding moieties simulated a multivalent ligand and promoted high-affinity, cooperative binding of the target molecule. Statistical calculations were applied to SAM components in solution and gold-sulfur packing dimensions to extract the inter-ligand-distance within the SAM. This distance information is valuable to the rational design of multivalent drugs.

1 . A method for presenting discrete binding moieties in a controlled geometry that promotes high-affinity, cooperative binding to a target molecule, comprising forming a self-assembled monolayer that incorporates at least one thiol species (the biospecific component) that is capable of directly or indirectly displaying a binding partner to said target molecule and at least one inert spacer thiol component by the process of: 
 (a) mixing the biospecific and a second component of said self-assembled monolayer in defined proportions; and    (b) forming said self-assembled monolayer on a suitable substrate.    
     
     
         2 - 39 . (canceled)