scholarly journals Two coexisting pseudo-mirror heteromolecular telomeric G-quadruplexes in opposite loop progressions differentially recognized by a low equivalent of Thioflavin T

2021 ◽  
Vol 49 (18) ◽  
pp. 10717-10734
Author(s):  
Wenqiang Fu ◽  
Haitao Jing ◽  
Xiaojuan Xu ◽  
Suping Xu ◽  
Tao Wang ◽  
...  

Abstract The final 3′-terminal residue of the telomeric DNA G-overhang is inherently less precise. Here, we describe how alteration of the last 3′-terminal base affects the mutual recognition between two different G-rich oligomers of human telomeric DNA in the formation of heteromolecular G-quadruplexes (hetero-GQs). Associations between three- and single-repeat fragments of human telomeric DNA, target d(GGGTTAGGGTTAGGG) and probe d(TAGGGT), in Na+ solution yield two coexisting forms of (3 + 1) hybrid hetero-GQs: the kinetically favourable LLP-form (left loop progression) and the thermodynamically controlled RLP-form (right loop progression). However, only the adoption of a single LLP-form has been previously reported between the same probe d(TAGGGT) and a target variant d(GGGTTAGGGTTAGGGT) having one extra 3′-end thymine. Moreover, the flanking base alterations of short G-rich probe variants also significantly affect the loop progressions of hetero-GQs. Although seemingly two pseudo-mirror counter partners, the RLP-form exhibits a preference over the LLP-form to be recognized by a low equivalent of fluorescence dye thioflavin T (ThT). To a greater extent, ThT preferentially binds to RLP hetero-GQ than with the corresponding telomeric DNA duplex context or several other representative unimolecular GQs.

2021 ◽  
Author(s):  
Ben Jia ◽  
Lan Jia ◽  
Jingxin Zhu

Abstract In this work, the potential application of the fluorescence dye Thioflavin-T (ThT), which can specifically bind to amyloid, as a powerful tool for monitoring secondary structure transitions of silk fibroin (SF) induced by pH was examined. Results showed that ThT emission intensities substantially increased when pH decreased from 6.8 to 4.8. This increase may be due to conformational transitions from random coil to β-sheet. The morphology and secondary structure of SF were also investigated via TEM, AFM and circular dichroism spectroscopy. The information obtained herein can be utilized not only for the development of convenient and efficient noninvasive method for monitoring the assembly behavior of SF in aqueous solution but also for in vitro fluorescence imaging.


2004 ◽  
Vol 44 (supplement) ◽  
pp. S116
Author(s):  
K. Morimoto ◽  
K. Kawabata ◽  
S. Kunii ◽  
K. Akasaka

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1010 ◽  
Author(s):  
Babitha Machireddy ◽  
Holli-Joi Sullivan ◽  
Chun Wu

Although BRACO19 is a potent G-quadruplex binder, its potential for clinical usage is hindered by its low selectivity towards DNA G-quadruplex over duplex. High-resolution structures of BRACO19 in complex with neither single-stranded telomeric DNA G-quadruplexes nor B-DNA duplex are available. In this study, the binding pathway of BRACO19 was probed by 27.5 µs molecular dynamics binding simulations with a free ligand (BRACO19) to a DNA duplex and three different topological folds of the human telomeric DNA G-quadruplex (parallel, anti-parallel and hybrid). The most stable binding modes were identified as end stacking and groove binding for the DNA G-quadruplexes and duplex, respectively. Among the three G-quadruplex topologies, the MM-GBSA binding energy analysis suggested that BRACO19′s binding to the parallel scaffold was most energetically favorable. The two lines of conflicting evidence plus our binding energy data suggest conformation-selection mechanism: the relative population shift of three scaffolds upon BRACO19 binding (i.e., an increase of population of parallel scaffold, a decrease of populations of antiparallel and/or hybrid scaffold). This hypothesis appears to be consistent with the fact that BRACO19 was specifically designed based on the structural requirements of the parallel scaffold and has since proven effective against a variety of cancer cell lines as well as toward a number of scaffolds. In addition, this binding mode is only slightly more favorable than BRACO19s binding to the duplex, explaining the low binding selectivity of BRACO19 to G-quadruplexes over duplex DNA. Our detailed analysis suggests that BRACO19′s groove binding mode may not be stable enough to maintain a prolonged binding event and that the groove binding mode may function as an intermediate state preceding a more energetically favorable end stacking pose; base flipping played an important role in enhancing binding interactions, an integral feature of an induced fit binding mechanism.


Author(s):  
Simon Morgan Wortham

This chapter concentrates on Fanon’s Black Skin, White Masks, where the Hegelian theme of mutual recognition as the origin of man’s self-consciousness and potential freedom is tested against the complex circumstances of colonialism. Fanon’s idea that the ‘Negro slave’ is recognized by the ‘White Master’ in a situation that is ‘without conflict’ suggests a possibly double, or self-resistant, meaning: the colonial situation after slavery ushers in something like a phony war; but also colonialism’s historical interpretation is not exhausted by the Hegelian master-slave logic. Through this double possibility of the colonial, one wonders whether after Hegel it is historical interpretation or the historical process itself that has gone awry. Such dynamic tensions suggest an impossibly divided dialectics at work throughout Fanon’s corpus. The section of Fanon’s ‘The Negro and Recognition’ devoted to a critique of Adler points to an earlier footnote in Black Skin, White Masks which offers a lengthy engagement with Lacan, allowing us to reread the politics of racial difference into the scene of the Lacanian mirror-stage. Here, the resistant ‘other’ of psychoanalysis unlocks the possibility of another ‘politics’ capable of addressing, by better recognising, some of its most significant impasses.


Trictrac ◽  
2018 ◽  
Vol 10 ◽  
Author(s):  
Petru Adrian Danciu

Starting from the cry of the seraphim in Isaiahʹ s prophecy, this article aims to follow the rhythm of the sacred harmony, transcending the symbols of the angelic world and of the divine names, to get to the face to face meeting between man and God, just as the seraphim, reflecting their existence, stand face to face. The finality of the sacred harmony is that, during the search for God inside the human being, He reveals Himself, which is the reason for the affirmation of “I Am that I Am.” Through its hypnotic cyclicality, the profane temporality has its own musicality. Its purpose is to incubate the unsuspected potencies of the beings “caught” in the material world. Due to the fact that it belongs to the aeonic time, the divine music will exceed in harmony the mechanical musicality of profane time, dilating and temporarily cancelling it. Isaiah is witness to such revelation offering access to the heavenly concert. He is witness to divine harmonies produced by two divine singers, whose musical history is presented in our article. The seraphim accompanied the chosen people after their exodus from Egypt. The cultic use of the trumpet is related to the characteristics and behaviour of the seraphim. The seraphic music does not belong to the Creator, but its lyrics speak about the presence of the Creator in two realities, a spiritual and a material one. Only the transcendence of the divine names that are sung/cried affirms a unique reality: God. The chant-cry is a divine invocation with a double aim. On the one hand, the angels and the people affirm God’s presence and call His name and, on the other, the Creator affirms His presence through the angels or in man, the one who is His image and His likeness. The divine music does not only create, it is also a means of communion, implementing the relation of man to God and, thus, God’s connection with man. It is a relation in which both filiation and paternity disappear inside the harmony of the mutual recognition produced by music, a reality much older than Adam’s language.


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