Mimotopes of the nicotinic receptor binding site selected by a combinatorial peptide library.

Abstract

Peptide libraries allow selecting new molecules, defined as mimotopes, which are able to mimic the structural and functional features of a native protein. This technology can be applied for the development of new reagents, which can interfere with the action of specific ligands on their target receptors. In the present study we used a combinatorial library approach to produce synthetic peptides mimicking the snake neurotoxin binding site of nicotinic receptors. On the basis of amino acid sequence comparison of different alpha-bungarotoxin binding receptors, we designed a 14 amino acid combinatorial synthetic peptide library with five invariant, four partially variant, and five totally variant positions. Peptides were synthesized using SPOT synthesis on cellulose membranes, and binding sequences were selected using biotinylated alpha-bungarotoxin. Each variant position was systematically identified, and all possible combinations of the best reacting amino acids in each variant position were tested. The best reactive sequences were identified, produced in soluble form, and tested in BIACORE to compare their kinetic constants. We identified several different peptides that can inhibit the binding of alpha-bungarotoxin to both muscle and neuronal nicotinic receptors. Peptide mimotopes have a toxin-binding affinity that is considerably higher than peptides reproducing native receptor sequences.

Statistics

01020'03'05'07'09'11'13'15'17
Citations per Year

53 Citations

Semantic Scholar estimates that this publication has 53 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Bracci2001MimotopesOT, title={Mimotopes of the nicotinic receptor binding site selected by a combinatorial peptide library.}, author={Luisa Bracci and Luisa Lozzi and Barbara Lelli and Antonella Pini and Paola Neri}, journal={Biochemistry}, year={2001}, volume={40 22}, pages={6611-9} }