To date, abundant information about the organization of ligand-binding sites of nicotinic acetylcholine receptors (nAChRs) is collected. However, still now in structure-functional studies are widely used their structural homologs, such as the acetylcholine-binding proteins, the extracellular domains of the receptor and even their fragments. We have attempted to design a similar model of nAChR on the basis of its fragment, so called C-loop forming part of the ligand-binding site, with the use of computer modeling techniques. As the basis it was taken a high-affinity peptide (HAP) developed in 2000-ies [Harel et al, Neuron, 2001], which possessed high affinity towards α-bungarotoxin (αBgt), a potent blocker of several nAChR subtypes, and imitated the C-loop in the crystal complex with αBgt. Our experiments, however, showed that HAP does not interact not only with cholinergic ligands of a different chemical nature, but does not bind even to α-cobratoxin which is very similar in structure and function to αBgt. Computer modeling was applied for choosing desirable mutations in HAP sequence to obtain the analogue with increased affinity for α-cobratoxin. As a result, 15 new peptide analogues were synthesized and studied for ability to form complex with αBgt and α-cobratoxin and conclusions on the appropriateness of using such peptide models instead of the full-size nAChRs were made.