Construction of peptides having molecular recognition ability by using novel α, α-disubstituted glycines

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In this research project, we have intended to develop new functional peptides containing α, α-disubstituted glycines as key components. Because the side chains of α, α-disubstituted glycines are very crowded, they restrict the conformational mobility of peptide backbones and thus, stabilize the preferred conformation of the peptides. We investigated synthesis, conformation and intermolecular interaction of various peptides containing α-aminoisobutyric acid (Aib), α, α-diphenylglycine (Dph), 9-amino-fluorene-9-carboxylic acid (Afc) and α, α-di (2-pyridyl)glycine (2Dpy).1.Tetrapeptides (Trp-Aib-Gly-Leu-NHAr) were synthesized, and were clarified to adopt β-turn stabilized by intramolecular hydrogen bonding and steric effect of Aib. The tetrapeptides bound quaternary ammonium salts as guests on the binding site composed of aromatic moieties at both terminals of the peptide, affording the 1 : 1 complex.2.Pentapeptides (Z-AA_1-AA_1-Dph-AA_3-AA_3-OMe) and hexapeptides (Z-AA_1-Dph-AA_3-AA_1-Dp … More h-AA_3-OMe) containing α, α-diphenylglycine (Dph) were synthesized. By the X-ray structural analysis and NMR analysis, the pentapeptides where AA_1=Aib, were revealed to adopt 3_<10>-helix, whether AA_3 is Gly or Aib. Hexapeptide formed the 1 : 1 complex with dodecyl pyridinium salt.3.Tripeptides (Z-AA_1-Afc-AA_3-OMe) and hexapeptides (Z-AA_1-Afc-AA_3-AA_1-Afc-AA_3-OMe) containing a novel α, α-disubstituted glycine, 9-aminofluorene-9-carboxylic acid (Afc), were synthesized using the Ugi reaction. Some hexapeptides also bound dodecyl pyridinium salt to make the 1 : 1 complex.4.We succeeded in the first synthesis of tripeptides (Z-AA_1-2Dpy-AA_3-OMe) containing α, α-di (2-pyridyl)glycine (2Dpy). These tripeptides adopt a novel conformation in which each nitrogen atom of two pyridine rings forms an intramolecular hydrogen bond with hydrogen atoms of two amides, respectively. Furthermore, the tripeptides afforded crystals of the 2 : 1 complex with Cu ion, and the crystal structure were clarified by X-ray analysis. Less