Unique Helical Triangle Molecular Geometry Induced by Dipole–Dipole Interactions

Abstract

Novel helix-peptide wheels, in which three helices were connected by using a template, were prepared, and the dipole-dipole interactions among the helices were studied in relation to the formation of a planar triangle structure containing three helices. The helical segments had a 3 10 -helix structure.13 C spin-lattice relaxation time (T 1 ) measurements showed that the helical segments had restricted mobility. Deuterium exchange rates of amide protons were accelerated in the helix-peptide wheels compared to the respective linear helix peptides, suggesting that there is torsion on the cylindrical shape. Therefore, the predominant structure of the helix-peptide wheels is a planar triangle in solution. Further, the triangle structure was successfully transferred onto a gold substrate.Nano-science using organic molecules has attracted much attention in various fields. One key factor for the development of nano-science is to prepare organic molecules with well-determined geometry in terms of regio-and stereo-specificity, configuration, and conformation. Recently, a trend to use larger molecules has become prominent in the field of materials science with the aim to produce high-performance and highly functional materials. However, it becomes difficult to control the structure of larger molecules. Advancements in covalent chemistry contribute greatly to the preparation of well-specified large molecules, but secondary interactions, such as hydrogen bonds, 1 electrostatic interaction, 2 and CH-interaction, 3 etc., are also helpful to regulate the molecular shape. In the present study, another secondary interaction, dipole-dipole interaction, was examined for geometry regulation of three helices in one molecule.Proteins are typical examples for molecular architecture with a highly regulated structure. In nature, helix bundles are a common motif in proteins, and exhibit a variety of physiological activities, such as acting as ion channels. On the other hand, a helix triangle, in which three peptide helices were connected in a cyclic way by covalent bonds to generate a planar structure, was prepared as an unprecedented helix assembly. 4 Interestingly, the cyclization yield of the linear three peptide helices connected in a series was relatively high, suggesting that the dipole-dipole interaction may promote the cyclization probability via an attractive electrostatic force between the Nterminal with a partial positive charge and the C-terminal with a partial negative charge of the linear precursor peptide. We, therefore, designed a new helix triangle without covalent bonds between the N-terminal and the C-terminal but with dipole-dipole interaction acting between them.The molecular structures of the helix-peptide wheel, in which three helical peptides were connected by using the template molecule 1,3,5-benzenetricarboxylic acid through amidebond formation with the side chains of the Lys residues located in the middle of the helical peptide chains, are shown in Fig. 1. The three helices either nonapeptide or hexapeptide can ...

The critical main‐chain length for helix formation in water: Determined in a peptide series with alternating Aib and Ala residues exclusively and detected with ECD spectroscopy

“…The onset of the α‐helix is first observed in the –(Ala–Aib) 5 – decapeptide 9. In alcohol solutions, the ECD signatures typical of the 3 10 ‐ and α‐helices are recognized at the heptamer and octamer levels, respectively 13–20…”

“…Using ECD spectroscopy,13–20 it was shown that in polar, hydrogen‐bonding donor, solvents such as methanol, ethanol, and 2,2,2‐trifluoroethanol (TFE), the characteristic features (double negative maxima near 222 and 205 nm) of a right‐handed helical conformation are first seen at the octapeptide –(Aib–Ala) 4 – or –(Ala–Aib) 4 –/nonapeptide –Ala–(Aib–Ala) 4 – levels. ECD patterns indicative of partially developed 3 10 ‐ and α‐helical conformations first appear at the 7‐ and 8‐mers, respectively.…”

“…In the last few years, Kimura and coworkers7, 15–20, 22–24 described the intriguing physicochemical properties of the alternating –(Ala–Aib) n – peptides. In particular, these authors reported the scientifically stimulating ability of their helical structures to transfer electrons to long distances (up to 120 Å), even through a self‐assembled monolayer on a gold surface.…”

Molecular dipole engineering: new aspects of molecular dipoles in molecular architecture and their functions

“…To answer this question, three helical peptides were bound to a template molecule through the middle residue of the helices. 6 The linker was long enough to allow them free rotation around the template. The helical nonapeptide, Boc-(Ala-Aib) 2 -Lys(X)-(Ala-Aib) 2 -OMe (X and Aib represent the template and 2-aminoisobutyric acid, respectively), was found to form a 3 10 helix due to the Aib residues.…”

Сhiral and Racemic Fields Concept for Understanding of the Homochirality Origin, Asymmetric Catalysis, Chiral Superstructure Formation from Achiral Molecules, and B-Z DNA Conformational Transition

“…Racemic superstructures formed by P-and M-helices represent a large group of racemates [39,[270][271][272]. There is no consensus about a reason for the structural difference between heterochiral (racemic) and homochiral dimers [273][274][275].…”