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

本研究以α，α-二取代甘氨酸为关键成分，开发新型功能肽。由于α，α-二取代甘氨酸的侧链非常拥挤，它们限制了肽骨架的构象移动性，从而稳定了肽的优选构象。研究了α-氨基异丁酸（Aib）、α，α-二苯基甘氨酸（Dph）、9-氨基芴-9-羧酸（Afc）和α，α-二（2-吡啶基）甘氨酸（2Dpy）等4种多肽的合成、构象和分子间相互作用。五肽（Z-AA_1-AA_1-Dph-AA_3-AA_3-OMe）和六肽（Z-AA_1-Dph-AA_3-AA_1-Dp）与季铵盐形成1：1的复合物 ...更多信息 合成了含α，α-二苯基甘氨酸（Dph）的α-AA_3-OMe。通过X-射线衍射和核磁共振分析，发现AA_1=Aib的五肽，<10>无论AA_3是Gly还是Aib，均采用3_ -螺旋结构。利用Ugi反应合成了含有新型α，α-二取代甘氨酸9-氨基芴-9-羧酸（Afc）的三肽（Z-AA_1-Afc-AA_3-OMe）和六肽（Z-AA_1-Afc-AA_3-AA_1-Afc-AA_3-OMe）。4.首次合成了含α，α-二（2-吡啶基）甘氨酸（2Dpy）的三肽（Z-AA_1-2Dpy-AA_3-OMe）。这些三肽采用一种新的构象，其中两个吡啶环的每个氮原子分别与两个酰胺的氢原子形成分子内氢键。此外，三肽与Cu离子形成2：1的配合物晶体，并通过X射线分析澄清晶体结构。少

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