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81.
82.
Triple helix formation with purine-rich phosphorothioate-containing oligonucleotides covalently linked to an acridine derivative. 总被引:4,自引:3,他引:1
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Purine-rich (GA)- and (GT)-containing oligophosphorothioates were investigated for their triplex-forming potential on a 23 bp DNA duplex target. In our system, GA-containing oligophosphorothioates (23mer GA-PS) were capable of triplex formation with binding affinities lower than (GA)-containing oligophosphodiesters (23mer GA-PO). The orientation of the third strand 23mers GA-PS and GA-PO was antiparallel to the purine strand of the duplex DNA target. In contrast, (GT)-containing oligophosphorothioates (23mer GT-PS) did not support triplex formation in either orientation, whereas the 23mer GT-PO oligophosphodiester demonstrated triplex formation in the antiparallel orientation. GA-PS oligonucleotides, in contrast to GT-PS oligonucleotides, were capable of self-association, but these self-associated structures exhibited lower stabilities than those formed with GA-PO oligonucleotides, suggesting that homoduplex formation (previously described for the 23mer GA-PO sequence by Noonberg et al.) could not fully account for the decrease in triplex stability when phosphorothioate linkages were used. The 23mer GA-PS oligonucleotide was covalently linked via its 5'-end to an acridine derivative (23mer Acr-GA-PS). In the presence of potassium cations, this conjugate demonstrated triplex formation with higher binding affinity than the unmodified 23mer GA-PS oligonucleotide and even than the 23mer GA-PO oligonucleotide. A (GA)-containing oligophosphodiester with two phosphorothioate linkages at both the 5'- and 3'-ends exhibited similar binding affinity to duplex DNA compared with the unmodified GA-PO oligophosphodiester. This capped oligonucleotide was more resistant to nucleases than the GA-PO oligomer and thus represents a good alternative for ex vivo applications of (GA)-containing, triplex-forming oligonucleotides, allowing a higher binding affinity for its duplex target without rapid cellular degradation. 相似文献
83.
A family of bis-[4′-Azido-2,2′:6′,2″-terpyridine platinum(II)] complexes with linear linkers of varying length have been synthesized. They have been designed to bis-intercalate into two DNA duplexes in close proximity, the azido groups allowing the sites of intercalation to be photoaffinity labeled. The linker to Pt(II) bonds are susceptible to cleavage by thiols and cyanide ion, which is a requirement for the intended method of analysis by 2D gel electrophoresis. 相似文献
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85.
A mixture of C28 and C29 sterols have been isolated from Leptosphaeria typhae grown in vitro on “oat water” and characterized by GLC and MS. Mono-, di- and tri-unsaturated sterols are present in the extracts of fungi cultivated both in the dark and in the light but the sterol composition is different. The influence of “oat water” on sterol structure has been determined by comparison with the sterols of the same fungus grown on synthetic medium in the dark. 相似文献
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88.
A Cordi J M Lacoste V Audinot M Millan 《Bioorganic & medicinal chemistry letters》1999,9(10):1409-1414
The in vitro activities of 3-hydroxy-imidazolidin-4-one derivatives demonstrated very restricted structure-activity relationships at the strychnine-insensitive glycine site of the NMDA receptor. The most active compound (3a) was completely unsubstituted and exhibited affinity and efficacy similar to that of D-cycloserine, the prototypical partial agonist at this site. 相似文献
89.
Ján Dupej Alizé Lacoste Jeanson Josef Pelikán Jaroslav Brůžek 《American journal of physical anthropology》2017,164(4):868-876
The understanding of locomotor patterns, activity schemes, and biological variations has been enhanced by the study of the geometrical properties and cortical bone thickness of the long bones measured using CT scan cross‐sections. With the development of scanning procedures, the internal architecture of the long bones can be explored along the entire diaphysis. Recently, several methods that map cortical thickness along the whole femoral diaphysis have been developed. Precise homology is vital for statistical examination of the data; however, the repeatability of these methods is unknown and some do not account for the curvature of the bones. We have designed a semiautomatic workflow that improves the morphometric analysis of cortical thickness, including robust data acquisition with minimal user interaction and considering the bone curvature. The proposed algorithm also performs automatic landmark refinement and rigid registration on the extracted morphometric maps of the cortical thickness. Because our algorithm automatically reslices the diaphysis into 100 cross‐sections along the medial axis and uses an adaptive thresholding method, it is usable on CT scans that contain soft tissues as well as on bones that have not been oriented specifically prior to scanning. Our approach exhibits considerable robustness to error in user‐supplied landmarks, suppresses distortion caused by the curvature of the bones, and calculates the curvature of the medial axis. 相似文献
90.
Elisabeth Lobner Anne-Sophie Humm Georg Mlynek Konstantin Kubinger Michael Kitzmüller Michael W. Traxlmayr 《MABS-AUSTIN》2017,9(7):1088-1104
Fcabs (Fc domain with antigen-binding sites) are promising novel therapeutics. By engineering of the C-terminal loops of the CH3 domains, 2 antigen binding sites can be inserted in close proximity. To elucidate the binding mode(s) between homodimeric Fcabs and small homodimeric antigens, the interaction between the Fcabs 448 and CT6 (having the AB, CD and EF loops and the C-termini engineered) with homodimeric VEGF was investigated. The crystal structures of these Fcabs, which form polymers with the antigen VEGF in solution, were determined. However, construction of heterodimeric Fcabs (JanusFcabs: one chain Fc-wt, one chain VEGF-binding) results in formation of distinct JanusFcab–VEGF complexes (2:1), which allowed elucidation of the crystal structure of the JanusCT6–VEGF complex at 2.15 Å resolution. VEGF binding to Janus448 and JanusCT6 is shown to be entropically unfavorable, but enthalpically favorable. Structure-function relationships are discussed with respect to Fcab design and engineering strategies. 相似文献