| 1. |
- Chandramohan, Arun, et al.
(författare)
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Design-rules for stapled peptides with in vivo activity and their application to Mdm2/X antagonists
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Although stapled α-helical peptides can address challenging targets, their advancement is impeded by poor understandings for making them cell permeable while avoiding off-target toxicities. By synthesizing >350 molecules, we present workflows for identifying stapled peptides against Mdm2(X) with in vivo activity and no off-target effects. Key insights include a clear correlation between lipophilicity and permeability, removal of positive charge to avoid off-target toxicities, judicious anionic residue placement to enhance solubility/behavior, optimization of C-terminal length/helicity to enhance potency, and optimization of staple type/number to avoid polypharmacology. Workflow application gives peptides with >292x improved cell proliferation potencies and no off-target cell proliferation effects ( > 3800x on-target index). Application of these ‘design rules’ to a distinct Mdm2(X) peptide series improves ( > 150x) cellular potencies and removes off-target toxicities. The outlined workflow should facilitate therapeutic impacts, especially for those targets such as Mdm2(X) that have hydrophobic interfaces and are targetable with a helical motif.
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| 2. |
- Sandberg, David J., 1985, et al.
(författare)
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Ethnic-Racial Identity and Attitude Change: Assessments of Outgroup and Diversity Attitudes among Adolescents in Sweden
- 2024
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Ingår i: Journal of Youth and Adolescence. - 0047-2891 .- 1573-6601.
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Tidskriftsartikel (refereegranskat)abstract
- Outgroup and diversity attitudes are important components of intercultural understanding and well-being. Despite the potential of ethnic-racial identity development as a means to foster positive outgroup and diversity attitudes, little is known about its effectiveness in rapidly diversifying contexts such as Sweden. This pre-registered study filled this gap by examining if adolescents taking part in an intervention focused on ethnic-racial identity exploration, the Identity Project, also reported change in outgroup and diversity attitudes, and whether migration background, education type, and ethnic-racial identity development predicted such change. Twenty-three tenth-grade classes in Sweden (N = 509; Mage = 16.28; SDage = 0.80; 66% female; 51% migration background) participated in the intervention and were assessed in four waves over a period of 26 weeks. Whereas ethnic-racial identity exploration and resolution increased for the intervention group, the adolescents reported no change in outgroup and diversity attitudes when compared to a control group. Increases in ethnic-racial identity exploration and resolution co-varied with increases in attitudes, but only at Time 3. The results do not provide support for the link between ethnic-racial identity development and positive outgroup and diversity attitudes, and challenge the notion of attitude change as a cascading effect of the Identity Project intervention in non-US sociocultural contexts. All aspects of the study were pre-registered on the Open Science Framework platform (https://osf.io/f5896).
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