First principles study on proton transfer between amino acid side chains of histidine and aspartic acid in β-structure

Partial molar volumes of the following mixtures, [Formula: see text](mix) were determined in water at 20 °C: (1) glutamic acid: glycine; (2) arginine:glycine; (3) arginine:glutamic acid; (4) arginine: aspartic acid; (5) lysine:glutamic acid, and (6) lysine: aspartic acid. Partial molar volumes of the mixtures calculated using [Formula: see text] of various ionic species of the amino acids agreed with the experimental values for systems 1 and 2, but were less than the experimental values for systems 3 to 6. The positive deviations, [Formula: see text] (mix), of the experimental values from the calculated values are discussed in terms of "specific interactions" between ionogenic side chains. The extent of interaction is greater in systems containing aspartic acid and/or arginine.

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Predicting the Strength of Stacking Interactions Between Heterocycles and Aromatic Amino Acid Side Chains

10.26434/chemrxiv.7628939.v2 ◽

2019 ◽

Author(s):

Andrea N. Bootsma ◽

Analise C. Doney ◽

Steven Wheeler

Keyword(s):

Amino Acid ◽

Binding Sites ◽

Aromatic Amino Acid ◽

Aromatic Amino Acids ◽

Biologically Active ◽

Side Chains ◽

Stacking Interactions ◽

Inhibitor Binding ◽

Protein Binding Sites ◽

Amino Acid Side Chains

Despite the ubiquity of stacking interactions between heterocycles and aromatic amino acids in biological systems, our ability to predict their strength, even qualitatively, is limited. Based on rigorous ab initio data, we have devised a simple predictive model of the strength of stacking interactions between heterocycles commonly found in biologically active molecules and the amino acid side chains Phe, Tyr, and Trp. This model provides rapid predictions of the stacking ability of a given heterocycle based on readily-computed heterocycle descriptors. We show that the values of these descriptors, and therefore the strength of stacking interactions with aromatic amino acid side chains, follow simple predictable trends and can be modulated by changing the number and distribution of heteroatoms within the heterocycle. This provides a simple conceptual model for understanding stacking interactions in protein binding sites and optimizing inhibitor binding in drug design.

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A Strategy for Thioamide Incorporation During Fmoc Solid-Phase Peptide Synthesis with Robust Stereochemical Integrity

10.26434/chemrxiv.8206247.v1 ◽

2019 ◽

Cited By ~ 1

Author(s):

luis camacho III ◽

Bryan J. Lampkin ◽

Brett VanVeller

Keyword(s):

Amino Acid ◽

Functional Groups ◽

Peptide Synthesis ◽

Solid Phase ◽

Solid Phase Peptide Synthesis ◽

Side Chains ◽

Amino Acid Side Chains ◽

Peptide Elongation

We describe a method to protect the sensitive stereochemistry of the thioamide—in analogy to the protection of the functional groups of amino acid side chains—in order to preserve the thioamide moiety during peptide elongation.

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