| 1. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
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| 7. |
- Pant, A., et al.
(författare)
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Allosteric Site Inhibitor Disrupting Auto-Processing of Malarial Cysteine Proteases
- 2018
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Falcipains are major haemoglobinases of Plasmodium falciparum required for parasite growth and development. They consist of pro- and mature domains that interact via 'hot-spot' interactions and maintain the structural integrity of enzyme in zymogen state. Upon sensing the acidic environment, these interactions dissociate and active enzyme is released. For inhibiting falcipains, several active site inhibitors exist, however, compounds that target via allosteric mechanism remains uncharacterized. Therefore, we designed and synthesized six azapeptide compounds, among which, NA-01 & NA-03 arrested parasite growth by specifically blocking the auto-processing of falcipains. Inhibitors showed high affinity for enzymes in presence of the prodomain without affecting the secondary structure. Binding of NA-03 at the interface induced rigidity in the prodomain preventing structural reorganization. We further reported a histidine-dependent activation of falcipain. Collectively, for the first time we provide a framework for blocking the allosteric site of crucial haemoglobinases of the human malaria parasite. Targeting the allosteric site could provide high selectivity and less vulnerable to drug resistance.
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| 8. |
- Patel, A., et al.
(författare)
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Strain-path controlled microstructure, texture and hardness evolution in cryo-deformed AlCoCrFeNi2.1 eutectic high entropy alloy
- 2018
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Ingår i: Intermetallics. - : Elsevier BV. - 0966-9795. ; 97, s. 12-21
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Tidskriftsartikel (refereegranskat)abstract
- The effect of strain path on microstructure, texture and hardness properties of AlCoCrFeNi 2.1 eutectic high entropy alloy containing ordered FCC (L1 2 ) and ordered BCC (B2) was investigated. The EHEA was cryo-rolled using UCR, MSCR (during which the samples were rotated by 90° around the ND between each pass) and TSCR(45°) (in which the samples were deformed by unidirectional rolling to half of the total strain and then diagonally rolled for rest half of the strain). The UCR processed material showed a rather heterogeneous microstructure. The textures of the L1 2 /FCC and B2 phases in the MSCR processed material agreed with the cross-rolling texture of the corresponding single phase materials, while the texture of the two phases in the TSCR(45°) processed materials appeared rather weak. Upon annealing at 800 °C, the UCR processed materials showed a novel heterogeneous microstructure, while the MSCR and TSCR(45°) processed materials revealed microduplex structure. The heterogeneous microstructure was replaced by the usual microduplex structure at higher annealing temperatures. The annealing texture of the L1 2 /FCC phase showed the presence of α-fiber (ND// < 011 > ) components while the B2 phase showed strong ND-fiber (ND// < 111 > ) components. The UCR processed material with novel heterogeneous microstructure showed much greater hardness as compared to the MSCR and TSCR(45°) processed materials. The present results indicate that strain path exerted significant influence in controlling microstructure, texture and hardness properties of EHEA.
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| 9. |
- Turner, S, et al.
(författare)
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Variants in genes coding for glutathione S-transferases and asthma outcomes in children
- 2018
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Ingår i: Pharmacogenomics. - : Future Medicine Ltd. - 1744-8042 .- 1462-2416. ; 19:8, s. 707-713
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Tidskriftsartikel (refereegranskat)abstract
- Our hypothesis was that children with mutations in genes coding for glutathione S-transferases (GST) have worse asthma outcomes compared with children with active type genotype. Data were collected in five populations. The rs1695 single nucleotide polymorphism (GSTP1) was determined in all cohorts (3692 children) and GSTM1 and GSTT1 null genotype were determined in three cohorts (2362 children). GSTT1 null (but not other genotypes) was associated with a minor increased risk for asthma attack and there were no significant associations between GST genotypes and asthma severity. Interactions between GST genotypes and SHS exposure or asthma severity with the study outcomes were nonsignificant. We find no convincing evidence that the GST genotypes studied are related to asthma outcomes.
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