Recognition and Stabilization of an α-Helical Peptide by a Synthetic Receptor

Alpha‐Helix Mimetics in Drug Discovery

“…Solvent mixture titrations in TFE/water demonstrated that helical stability is highest for the peptide having a pair of modified residues at the i and i þ 4 positions. Using an intermolecular hydrogen-bonding strategy, the same group has shown in several studies that guanidinium-based receptors can recognize aspartate residues at multiple i and i þ 3 or i þ 4 positions and induce a-helix formation (Peczuh and Hamilton, 2000;Peczuh et al, 1997). Scholtz et al (1993) showed that the (i, i þ 3) and (i, i þ 4) Glu-Lys interactions (6) are 11.2 CONSTRAINED PEPTIDES THAT ADOPT a-HELICAL CONFORMATIONS helix-stabilizing and are similar to each other in strength, regardless of the orientation of the side chains.…”

Choline Esterase Inhibitors and Synthetic Oxalic Acid Receptors Based on Calix[4]arene Derivatives

“…A series of new distally disubstituted calix [4]arenes were prepared in 60 380% yields. Some of these compounds showed properties of reversible choline esterase effectors, activating it at low concentrations and inhibiting at high concentrations.…”

“…Transformation of the genetic information into such cell functions as growth activation and regulation of enzymes [1] is based on recognition and selective binding of the protein surface with biopolymers. Active studies made in the past decade are aimed at development of synthetic small molecules whose target is protein3 protein interaction [2, 3].Relatively simple and synthetically accessible molecules capable to reversibly [switch] various functions of proteins are interesting as potential components of drugs enhancing the specificity of the active component and its selective transport in patient's body [4]. However, the high degree of solvation and large area of the protein surface complicate the designing of molecules capable to reversibly alter the protein function.…”

“…Dicarboxylic acid I was prepared by hydrolysis of the corresponding ester. Compounds II3IV were prepared by selective alkylation of p-tert-butylcalix [4]arene with the corresponding halo derivatives in acetonitrile in the presence of potassium carbonate. …”

“…Relatively simple and synthetically accessible molecules capable to reversibly [switch] various functions of proteins are interesting as potential components of drugs enhancing the specificity of the active component and its selective transport in patient's body [4]. However, the high degree of solvation and large area of the protein surface complicate the designing of molecules capable to reversibly alter the protein function.…”