Interaction between Quaternary Ammonium Ions and Dipeptides: Positive Anion Allosteric Effect

Abstract

Noncovalent interactions are of fundamental importance in determining the highly dimensional structures and fundamental properties of molecular systems in biology, chemistry, and materials sciences. Relatively strong non-covalent bonding such as salt bridge and hydrogen bonding has been extensively investigated. In contrast, weak noncovalent bonding such as p-p, CH-p and cation-p interaction is now known to play important roles in the stabilization of the complexes 1-3) but is not well understood, because the weak noncovalent bond is usually cancelled behind the strong noncovalent bonding. However, there is much attention on cation-p interaction in a biological event such as recognition of biological relevant quaternary ammonium ions, for example, the neurotransmitter acetylcholine, by receptors and enzyme.4) Therefore, several research groups have devoted considerable effort to the synthesis of receptor molecules to investigate binding properties of quaternary ammonium cations. [5][6][7][8][9][10] In spite of many reports of synthetic receptors for binding quaternary ammonium ions, we are unaware of any on acyclic compounds acting as a receptor.11) Recently, we reported a study on the recognition of quaternary ammonium ion using acyclic phenol-formaldehyde dimer as a receptor, and found that quaternary ammonium cation is entrapped in the p cavity which is constructed of two phenol units; its counter ion participates in the recognition process by coordination via hydrogen bonding of the two hydroxyl groups. 12)As part of this study, we investigated the interaction between quaternary ammonium ions and dipeptides having the aromatic amino acid residues tyrosine and tryptophane, which have exchangeable protons (OH and NH) and aromatic surfaces.Dipeptides (1) were prepared in good yield by the condensation reactions of N-Boc L-amino acid with L-amino acid methyl ester monohydrochloride in the presence of N-methyl morphorine in CHCl 3 using DCC (1,3-dicyclohexylcarbodiimide) as a condensation reagent according to the literature (Fig. 1). 13)The interaction behavior of dipeptides (1) and quaternary ammonium ions (2) was studied by using 1 H-NMR spectroscopy at 20°C. When benzyl trimethyl ammonium chloride (2a) was added into a CDCl 3 solution of Boc-Tyr-TyrOMe (1a) at the ratio of 1a : 2aϭ1 : 1 ([1]ϭ[2]ϭ10 mM), all peaks of 2a moved to a higher field due to the ring current effect of the aromatic rings of 1a during formation of the complex as shown in Fig. 2. Especially, higher induced chemical shifts of the N ϩ -CH 2 and N ϩ -CH 3 protons of 2a were observed, suggesting that the ammonium moiety is located close to the aromatic surface of 1a.5-12) The same phenomenon was also observed in the mixture of Boc-Trp-Trp-OMe (1b) and 2a in CDCl 3 . In contrast, the chemical shifts of 2a scarcely changed in the presence of Boc-Phe-Phe-OMe (1c), indicating that no complexation occurs between 1c and 2a. Although Boc-Tyr-Phe-OMe (1d) and Boc-Trp-Phe-OMe (1e) having a phenol or an indole group can interact with ammonium ion (2a),...

The Effect of Counterion and Tertiary Amine on the Efficiency of N‐Triazinylammonium Sulfonates in Solution and Solid‐Phase Peptide Synthesis

“…Herein, we present a systematic study in order to establish how modifications of the tertiary amine component and counterion could influence the stability, versatility and coupling efficiency of this family of coupling reagents. This proposition was additionally supported by the previously reported influence of the counterion on the stability of coupling reagents19a as well as disruption of the peptide chain conformation in the presence of the ions 19b…”

The Minimal Pharmacophore for Silent Agonism of the α7 Nicotinic Acetylcholine Receptor

“…(2-Hydroxyethyl)-triethylammonium iodide [(2OHE)-triEA] (Kasuga et al, 1969) was made from 2-diethylaminoethanol and ethyl iodide, and is a white solid. Benzyltrimethylammonium iodide (BtriMA) (Ito et al, 2005) was made from dimethylbenzylamine and methyl iodide, and is a white solid. Benzylethyldimethylammonium iodide (BEdiMA) (Short and Biermacher, 1962) was made from dimethylbenzylamine and ethyl iodide, and is a white hygroscopic solid.…”

The Cation−π Interaction at Protein–Protein Interaction Interfaces: Developing and Learning from Synthetic Mimics of Proteins That Bind Methylated Lysines

“…Previous work using dipeptides as synthetic hosts has shown that they can bind ammonium cations in chloroform. 38 Moderate affinity between a tyrosinebased dipeptide host and acetylcholine were measured in chloroform (K d = 7.69 mM). We created new hosts based on this synthetic scaffold with two key features: the addition of carboxylates for improved electrostatic attraction and water solubility and the introduction of indole-N-benzyl substituents as additional aromatic surfaces for cation binding ( Figure 4).…”