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Is this idea of mass frustration distinctly Korean, or is it more international in scope? In her ongoing column on untranslatable words, Veronica Esposito looks at han, including how it [...]

IN THIS ONGOING feature, Veronica Esposito interviews emerging translators who are changing the way we read world literature and beginning to reshape the translation field. While opening bookstores, leading national [...]

Cystatins are small proteins, typically composed of 100–120 amino acids, which together with similar proteins devoid of inhibitory properties, belong to a cystatin ‘superfamily’. Cystatins can do more than just inhibit proteases: two important aspects described here are aggregation properties linked to misfolding diseases and the unique ability of monellin, a plant cystatin, to elicit sweet taste. The explanation of the puzzling phenomenon of ‘sweet proteins’ required an in-depth structural study of monellin, also regarding the causes of the high thermal stability of its single chain structure. The detailed mechanisms by which cystatins aggregate could be relevant in the study of misfolding diseases involving cystatins. They are reviewed here with emphasis on 3D domain swapping, typical of aggregating cystatins. While studying monellin, we noticed that it aggregates in a conventional way, probably through the cross-β spine mechanism. However, several cystatins derived from oryzacystatin_I to emulate the taste behavior of monellin aggregate via different mechanisms.

In this paper, we study the T30923 antiproliferative potential and the contribution of its loop residues in six different human cancer cell lines by preparing five T30923 variants using the single residue replacement approach of loop thymidine with an abasic site mimic (S). G-rich oligonucleotides (GRO) show interesting anticancer properties because of their capability to adopt G-quadruplex structures (G4s), such as the G4 HIV-1 integrase inhibitor T30923. Considering the multi-targeted effects of G4-aptamers and the limited number of cancer cell lines tested, particularly for T30923, it should be important to find a suitable tumor line, in addition to considering that the effects also strictly depend on G4s. CD, NMR and non-denaturating polyacrylamide gel electrophoresis data clearly show that all modified ODNs closely resemble the dimeric structure of parallel G4s' parent aptamer, keeping the resistance in biological environments substantially unchanged, as shown by nuclease stability assay. The antiproliferative effects of T30923 and its variants are tried in vitro by MTT assays, showing interesting cytotoxic activity, depending on time and dose, for all G4s, especially in MDA-MB-231 cells with a reduction in cell viability approximately up to 30%. Among all derivatives, QS12 results are the most promising, showing more pronounced cytotoxic effects both in MDA-MB-231 and Hela cells, with a decrease in cell viability from 70% to 60%. In summary, the single loop residue S substitution approach may be useful for designing antiproliferative G4s, considering that most of them, characterized by single residue loops, may be able to bind different targets in several cancer cell pathways. Generally, this approach could be of benefit by revealing some minimal functional structures, stimulating further studies aimed at the development of novel anticancer drugs. [ABSTRACT FROM AUTHOR]

The study employs off-resonance relaxation NMR spectroscopy to report the saturation difference transfer involved in the formation of amyloid [beta]-peptide (A[beta]) fibrils in human plasma by using the human serum albumin (HSA). The analysis reveals that the described model is widely used to cure Alzheimer's disease, in addition to its ability of investigating the mechanism of action of other oligomerization inhibitors of other amyloidogenic systems as well.

The thermodynamic and kinetic properties of peptide nucleic acid (PNA)-DNA chimeric strands to assemble in quadruplex structures are determined by CD spectroscopy and differential scanning calorimetry (DSC). The ability of PNA-DNA chimeras to form stable quadruplex structures helps in designing better therapeutic agents.

Telomeres are DNA protein structures, which comprise noncoding repeats of guanine-rich sequences. The thermodynamic parameters of these quadruplexes are determined.