A simple two-armed receptor has been prepared that binds certain peptides sequence-selectively in water at pH 4. 0 1997 Elsevier Science Ltd.
Significant progress is being made in the design and preparation of sequence-selective synthetic receptors for peptides. 1 While the original peptide-binding receptors had complex, cage-like structures characteristic of typical host molecules, simpler structures have recently been found that also possess highly sequence-selective peptide-binding properties. The way we identify such structures involves the synthesis of prototypes of given receptor designs and then screening those prototypes for binding with a large combinatorial library of peptides. We are looking for those designs that not only bind peptides but also tend to bind them with high sequence-selectively. The ultimate objective is to identify receptor designs that can be prepared as large combinatorial libraries so that highly selective receptors for any given peptidic (or other) substrate can be selected from the library.
One class of simple peptide-binding molecules has been described as a "two-armed receptor" and its general structure is sketched below. In this structure, the linker is typically a conformationally restricted moiety that covalently bonds and directs two functionalized, substrate-binding arms toward one another to form a binding cleft.2>3 While the general diagram below could well be applied to many well-known C2symmetric chiral reagents and tweezer-like host molecules, 4 there is no need that the two arms be identical and, indeed, one of the main attractions of this motif is its use in libraries of unsymmetrical two-armed receptors that could be assembled combinatorially from a diverse set of linkers and arms.
R
Dye-N
Two-Armed Receptor
One two-armed receptor we have studied extensively is shown above as 1 and its arms are macrocyclic oligomers of isophthalic acids (A, A') and trans-1,2-diaminocyclohexane (B). The Dye is used as a label to allow direct observation of the binding of 1 to substrates (e.g. peptides) attached to solid support particles (e.g. Metrifield synthesis beads). We have prepared a number of related molecules and