Aromatic-amide interactions

From the comparative experiments in DjO the catalysis by the cyclic dipeptides was confirmed to be nucleophilic, which is the same as the imidazole catalysis. It is seen in Table 16 that in the hydrolysis of PNPA kc for the cyclic peptides is onfy 1/10-1/5 as much as that for imidazole. The lower reactivity of the cyclic dipeptides is explained partly in terms of the lower pKj values and partly because of the larger steric hindrance for the nucleophilic reaction. Only when the pattern of the substrate binding—intramolecular catalysis of the cyclic peptides excels the decrease of basicity and the increase of steric hindrance, an enhanced catalysis by the cyclic dipeptides is possible. With regard to an increase of reactivity was expected for the hydro-phobic interactions by a sli tly larger acyl chain and for the aromatic-amide interaction (see Sections 3.3 and 3.6) between the p-phenyl group of the substrate and... 

Later, the conformation of Cydo-(Tyr-His) in DjO was investigated by NMR spectroscopy (75). Analyds of the NMR data according to the principle described in Section 3.6 showed that the phenol side diain of tyro l residue stacks over the diketopiperazine ring. Due to the aromatic-amide interactions, the internal rotation arcMind the Tyr-C -< bond is stabilized. Furthermore,/h-c -cP-h Wsti-... 

Local structure due to an aromatic-amide interaction observed by proton nuclear magnetic resonance spectroscopy in peptides related to the N terminus of bovine pancreatic trypsin inhibitor. J. Mol. Biol. 230 312-322. 

If the interaction sites are not present in the solute, they must be added through derivatization. When derivatization is required, the standard approach is to convert an alcohol, amine, or carboxylic acid to an aromatic amide, urea, or carbamate. For example, amphetamine was resolved as its naphthoyl amide (21), a series of ot-methylaryl acetic acid antiinflammatory agents were resolved after conversion to their 1-naphthalenemethyl-amides (22), and aliphatic alcohols can be resolved as 3,5-dinitro-carbamates (23). Other derivatives such as oxazolidones (24) and oxazolidines (25) have also been used. 

The amide solvent serves also as an acid acceptor for the hydrogen chloride produced in the reaction. Other polar aprotic solvents such as dimethyl-formamide (DMF) and dimethylsulfoxide (DMSO) cannot be used because they react significantly with acid chlorides [Id]. Amide solvents can interact efficiently with the aromatic amide polymers of moderately high molecular weight formed during the condensation reaction, and therefore provide maximum swelling. Consequently this allows the macromolecular chain to continue to grow until completion. Many of the key factors required in polycondensation... 

The CHARMm force field [20] was developed particularly for biological macromolecules, and has become a main force field for investigating biological systems. Kollman and co-workers [21,22] have fitted the benzene-cation interaction very accurately with fliree-body term force fields by including polarizability. Weaver and Donini [23] have also validated the applicability of CHARMm for benzene-cation interaction. Therefore, this study focuses on the aromatic-aliphatic, aromatic-aromatic, aromatic-amide(S), aromatic-amide(B), aromatic-thiol, aromatic-amine, and aromatic-alcohol interactions. 

As will be shown, the original CHARMm parameters can produce IPESs in good agreement with those calculated by the CP-corrected MP2 method for aromatic-aliphatic, aromatic-amide(S), and aromatic-amide(B) interactions. However, for aromatic-aromatic, aromatic-thiol, aromatic-amine, and aromatic-alcohol interactions, the original parameters cannot reproduce the IPESs which match CP-corrected MP2 results. Therefore, the Lennard-Jones parameters for the important atom pair in these four interactions were selected to be optimized. The original and optimized CHARMm Lennard-Jones parameters for these chosen atom pairs are collected in Table 1 for each of these four interactions. 

For each of these 38 calculated configurations, the difference in the magnitudes between the CHARMm and MP2 stabilization energy is less than 0.53 kcal/mol. Therefore, the existing CHARMm force field is qualified for the aromatic-amide(B) interaction. 

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