Insights into eukaryotic evolution from transmembrane domain lengths

<p>Biological membranes, comprised of proteins anchored by their trans-membrane domains (TMDs) creating a semi-permeable phase with lipid constituents, serve as ‘checkposts’ for not only intracellular trafficking in eukaryotic cells but also for material transactions of all living cells with external environments. Hydropathy (or hydrophobicity) plots of ‘bitopic’ proteins (i.e. having single alpha-helical TMDs) are routinely utilized in biochemistry texts for predicting their TMDs. The number of amino acids (i.e. TMD length) embedded as alpha-helices may serve as indicators of thickness of biological membranes in which they reside under assumptions that are universally applied for fixing window sizes for identifying TMDs using hydropathy plots. In this work we explore variations in thickness of different eukaryotic biological membranes (reflected by TMD lengths of their resident proteins) over evolutionary time scales. Rigorous <i>in silico</i> analyses of over 23,000 non-redundant membrane proteins residing in different subcellular locations from over 200 genomes of fungi, plants, non-mammalian vertebrates and mammals, reveal that differences in plasma membrane and organellar TMD lengths have decreased over time (scales) of eukaryotic cellular evolution. While earlier work has indicated decreasing differences in TMD lengths with increasing ‘perceived’ organismal complexity, this work is the first report on TMD length variations as a function of evolutionary time of eukaryotic cellular systems. We report that differences in TMD lengths of bitopic proteins residing in plasma membranes and other intra-cellular locations have decreased with evolutionary time, suggesting better/more avenues of intracellular trafficking in the emergence of eukaryotic organisms.</p

Visible Light-Prompted Regioselective Synthesis of Novel 5‑Aroyl/hetaroyl-2′,4-dimethyl-2,4′-bithiazoles as DNA- and BSA-Targeting Agents

Organic transformations mediated by visible light have gained popularity in recent years as they are green, renewable, inexpensive, and clean and yield excellent products. The present study describes cyclo-condensation of 2-methylthiazole-4-carbothioamide with differently substituted α-bromo-1,3-diketones achieved by utilizing a white light-emitting diode (LED) (9W) to accomplish the regioselective synthesis of novel 5-aroyl/hetaroyl-2′,4-dimethyl-2,4′-bithiazole derivatives as DNA/bovine serum albumin (BSA)-targeting agents. The structure characterization of the exact regioisomer was achieved unequivocally by heteronuclear two-dimensional nuclear magnetic resonance (2D-NMR) spectroscopy [1H–13C] HMBC; [1H–13C] HMQC; and [1H–15N] HMBC. In silico toxicity studies indicated that the synthesized compounds exhibit low toxicity risks and adhere to the rules of oral bioavailability without any exception. Computational molecular modeling of the bithiazole derivatives with the dodecamer sequence of the DNA duplex and BSA identified 5-(4-chlorobenzoyl)-2′,4-dimethyl-2,4′-bithiazole 7g as the most suitable derivative that can interact effectively with these biomolecules. Furthermore, theoretical results concurred with the ex vivo binding mode of the 7g with calf thymus DNA (ct-DNA) and BSA through a variety of spectroscopic techniques, viz., ultraviolet–visible (UV–visible), circular dichroism (CD), steady-state fluorescence, and competitive displacement assay, along with viscosity measurements

Facile, catalyst-free, microwave-assisted access toward the synthesis of 2-aryl/alkyl-3-(1<i>H</i>-benzo[<i>d</i>]imidazol-2-yl)-2, 3-dihydroquinazolin-4(1<i>H</i>)-ones

<p>An efficient, catalyst-free, microwave-assisted approach has been developed for the synthesis of 2-aryl/alkyl-3-(1<i>H</i>-benzo[<i>d</i>]imidazol-2-yl)-2,3-dihydroquinazolin-4(1<i>H</i>)-one derivatives by condensing 2-aminobenzamides with various aliphatic, aromatic, and heterocyclic aldehydes. This catalyst-free approach exhibited good functional group compatibility and produced the desired products in good to excellent yields in just 10–20 min. This approach can be seen as a better alternative of the metal-catalyzed protocols used for the synthesis of this class of compounds. The formation of desired compound has also been confirmed by X-ray analysis.</p