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N-Alkylated oligo- and poly(p-benzamide)s exist as dynamic helical structures with all-cis amide conformation. Imidazole N-alkylated amides also show cis conformational preference, but their major conformer is changed from cis to trans by addition of acid. Here, based on those findings, we designed and synthesized aromatic triamides 3 and hexaamides 4 containing an imidazole ring as candidate foldamers anticipated to exhibit acidinduced conformational change. X-ray structure analysis of oligomer 3c showed that it takes all-cis conformation in the crystal. In solution, all the oligoamides examined existed as an equilibrium mixture of 4 conformers, among which the major conformer was the folded all-cis structure as judged from the low-temperature ¹H NMR spectra. When trifluoroacetic acid-d was added to a solution of the oligoamides in methylene chlorided2, only 2 conformers were observed in the low-temperature ¹H NMR spectra, and the major conformer was the (trans, cis) form with respect to the amide bonds of the imidazole at the 4 and 2 positions. Experimental and theoretical analysis of the CD spectra indicated that the conformation of hexaamides 4 changes upon the addition of acid. Our results suggest that N-alkylated imidazole amide can serve as a key structural motif for the construction of foldamers with acid-switchable conformation. [ABSTRACT FROM AUTHOR]

Objectives: To prospectively evaluate the efficacy and tolerability of a six-week extended dosing interval with tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in sustained remission. Methods: Patients who received over six doses of intravenous TCZ in clinical remission (disease activity score [DAS] 28 - erythrocyte sedimentation rate [ESR] -2.6) maintained over 3 months between December 2013 and December 2015 were included. Flare was defined as DAS28-ESR >3.2 at two consecutive visits. Results: Twenty-five patients were enrolled; 87.5% achieved clinical remission at week 54 after sixweek extension and 95.5% achieved a van der Heijde modified total Sharp score (DmTSS) -0.5. The Health Assessment Questionnaire Disability Index (HAQ-DI) did not increase during 54 weeks. HAQ-DI at baseline and DDAS28-ESR at week six positively correlated with increase in DAS28-ESR at week 54. DSwollen joint count at week six positively correlated with DmTSS at week 54. A total of 12 adverse events occurring in 10 patients did not lead to cessation of TCZ except for one case of recurrent lymphoproliferative disorder at week five. Conclusion: A six-week extended dosing interval of TCZ for patients with RA in sustained remission is proposed as an acceptable treatment option for maintaining efficacy and tolerability. [ABSTRACT FROM AUTHOR]

The authors focus on a study related to the analysis of plastidic phosphate translocators present in the Mesembryanthemum crystallinum, an inducible crassulacean acid metabolism (CAM) plant. They inform that substrate specificities of the phosphoenolpyruvate/phosphate translocator, the triose phosphate/phosphate translocator and the glucose 6-phosphate/phosphate translocator ((McGPTl and McGPT2) are similar to that of orthologs. They mention that expression of McGPT2 is specific to CAM.