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- Andersson, H.O., et al.
(författare)
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Optimization of P1-P3 groups in symmetric and asymmetric HIV-1 protease inhibitors
- 2003
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Ingår i: European Journal of Biochemistry. - : Wiley. - 0014-2956 .- 1432-1033. ; 270:8, s. 1746-1758
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Tidskriftsartikel (refereegranskat)abstract
- HIV-1 protease is an important target for treatment of AIDS, and efficient drugs have been developed. However, the resistance and negative side effects of the current drugs has necessitated the development of new compounds with different binding patterns. In this study, nine C-terminally duplicated HIV-1 protease inhibitors were cocrystallised with the enzyme, the crystal structures analysed at 1.8-2.3 Å resolution, and the inhibitory activity of the compounds characterized in order to evaluate the effects of the individual modifications. These compounds comprise two central hydroxy groups that mimic the geminal hydroxy groups of a cleavage-reaction intermediate. One of the hydroxy groups is located between the d-oxygen atoms of the two catalytic aspartic acid residues, and the other in the gauche position relative to the first. The asymmetric binding of the two central inhibitory hydroxyls induced a small deviation from exact C2 symmetry in the whole enzyme-inhibitor complex. The study shows that the protease molecule could accommodate its structure to different sizes of the P2/P2' groups. The structural alterations were, however, relatively conservative and limited. The binding capacity of the S3/S3' sites was exploited by elongation of the compounds with groups in the P3/P3' positions or by extension of the P1/P1' groups. Furthermore, water molecules were shown to be important binding links between the protease and the inhibitors. This study produced a number of inhibitors with Ki values in the 100 picomolar range.
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| 4. |
- Svedlund, Marianne, et al.
(författare)
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Women’s narratives during the acute phase of their myocardial infarction
- 2001
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Ingår i: Journal of Advanced Nursing. - : Wiley. - 0309-2402 .- 1365-2648. ; 35:2, s. 197-205
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Tidskriftsartikel (refereegranskat)abstract
- Aim. The purpose of this study was to illuminate the meaning of lived experiences during the acute phase of an acute myocardial infarction (AMI). Method. Ten women (< 60 years old) afflicted with AMI narrated their experiences during their stay in the coronary care unit (CCU). The interview texts were interpreted using a method with a phenomenological hermeneutic approach, inspired by the philosophy of Ricoeur. The text was divided into meaning units that were condensed and abstracted. Three themes were then extracted from the text. Findings. One theme was ‘oneself as vulnerable’ with the subthemes: ‘the feeling of being dependent upon others’, ‘the feeling of being insulted’ and ‘the feeling of being a troublesome person’. Another theme was ‘oneself as distanced’, with the subthemes: ‘not facing the reality’, ‘captive in an unreal situation’, and ‘inhibition out of concern for others’. The last theme was: ‘oneself as making sense’ with the subthemes: ‘acquirement of some insight’ and ‘discovery of a new meaning with life’. Conclusion. The reported comprehensive understanding revealed the phenomena guilt and shame. These, in combination with the experience of being in an unreal situation and the withholding of feelings may have led to a deterioration of communication. It seems that relatives and the staff at CCU were not allowed to share the burden of being afflicted with an AMI.
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