| 1. |
|
|
| 2. |
- Almhöjd, Ulrica S., et al.
(författare)
-
Analysis of carious dentine using FTIR and ToF-SIMS.
- 2014
-
Ingår i: Journal of Oral Health and Dental Management. - 1583-5588. ; 13:3, s. 735-744
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract Apart from the Maillard reaction, other processes, such as esterification, take place in carious tissue. The aim of the present study was to analyse sound and carious dentine in terms of ester groups and their reaction with hydrazine derivate using Fourier Transform Infrared Spectroscopy (FTIR) and Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS). Carious and sound dentine from human premolars were excavated in three series (Experimental Parts I-III) and separated into inner and outer layers of carious dentine. The excavated tooth material was analysed with FTIR (Part I). Carious and sound dentine were also exposed to different chemical treatments and analysed with FTIR-Attenuated Total Reflectance (FTIR-ATR; Part II) and ToF-SIMS (Part III). The FTIR absorption spectra showed that the carious tissue contained ester groups, not detected in sound dentine. The results also indicated a higher occurrence of ester groups in the inner dental caries layer than in the outer ones. Potential binding to these ester groups by hydrazine derivative was observed after different chemical treatments with both FTIR-ATR and ToF-SIMS. The results of the present study revealed ester groups unique to the carious dentine which, after reaction with hydrazine derivative, form a covalent bond not found in sound dentine. The staining of carious unique groups would be clinically helpful in detection and prevention unnecessary removal of sound dentine.
|
|
| 3. |
- Altaib, Mohamed S., et al.
(författare)
-
Synthesis and NMR elucidation of novel pentacycloundecane-based peptides
- 2010
-
Ingår i: Magnetic Resonance in Chemistry. - : Wiley. - 0749-1581 .- 1097-458X. ; 48:6, s. 435-442
-
Tidskriftsartikel (refereegranskat)abstract
- The synthesis and NMR elucidation of two novel pentacycloundecane (PCU)-based peptides are reported. The PCU cage amino acids were synthesised as racemates and the incorporation of the cage amino acid with (S)-natural amino acids produced diastereomeric peptides. The diastereomeric 'cage' peptides were separated using preparative HPLC and the NMR elucidation of these PCU containing peptides are reported for the first time. The H-1 and C-13 NMR spectra showed series of overlapping signals of the cage skeleton and that of the peptide, making it extremely difficult to resolve the structure using one-dimensional NMR techniques only. The use of two-dimensional NMR techniques proved to be a highly effective tool in overcoming this problem.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Honarparvar, Bahareh, et al.
(författare)
-
Pentacycloundecane-diol-Based HIV-1 Protease Inhibitors : Biological Screening, 2D NMR, and Molecular Simulation Studies
- 2012
-
Ingår i: ChemMedChem. - : Wiley. - 1860-7179 .- 1860-7187. ; 7:6, s. 1009-1019
-
Tidskriftsartikel (refereegranskat)abstract
- Novel compounds incorporating a pentacycloundecane (PCU) diol moiety were designed, synthesized, and evaluated as inhibitors of the wild-type C-South African (C-SA) HIV-1 protease. Seven compounds are reported herein, three of which displayed IC50 values in the 0.50.6 mu M range. The cytotoxicity of PCU cage peptides toward human MT-4 cells appears to be several orders of magnitude less toxic than the current antiviral medications ritonavir and lopinavir. NMR studies based on the observed through-space 1H,1H distances/contacts in the EASY-ROESY spectra of three of the considered PCU peptide inhibitors enabled us to describe their secondary solution structure. Conserved hydrogen bonding interactions were observed between the hydroxy group of the PCU diol inhibitors and the catalytic triad (Asp25, Ile26, Gly27) of HIV protease in docking and molecular dynamics simulations. The biological significance and possible mode of inhibition by PCU-based HIV protease inhibitors discussed herein facilitates a deeper understanding of this family of inhibitors and their potential application to a vast number of alternative diseases related to proteases.
|
|
| 8. |
|
|
| 9. |
- Makatini, Maya M., et al.
(författare)
-
Pentacycloundecane-based inhibitors of wild-type C-South African HIV-protease
- 2011
-
Ingår i: Bioorganic & Medicinal Chemistry Letters. - : Elsevier BV. - 0960-894X .- 1464-3405. ; 21:8, s. 2274-2277
-
Tidskriftsartikel (refereegranskat)abstract
- In this study, we present the first account of pentacycloundecane (PCU) peptide based HIV-protease inhibitors. The inhibitor exhibiting the highest activity made use of a natural HIV-protease substrate peptide sequence, that is, attached to the cage (PCU-EAIS). This compound showed nanomolar IC50 activity against the resistance-prone wild type C-South African HIV-protease (C-SA) catalytic site via a norstatine type functional group of the PCU hydroxy lactam. NMR was employed to determine a logical correlation between the inhibitory concentration (IC50) results and the 3D structure of the corresponding inhibitors in solution. NMR investigations indicated that the activity is related to the chirality of the PCU moiety and its ability to induce conformations of the coupled peptide side chain. The results from docking experiments coincided with the experimental observed activities. These findings open up useful applications for this family of cage peptide inhibitors, considering the vast number of alternative disease related proteases that exist.
|
|
| 10. |
- Makatini, Maya M., et al.
(författare)
-
Synthesis, 2D-NMR and molecular modelling studies of pentacycloundecane lactam-peptides and peptoids as potential HIV-1 wild type C-SA protease inhibitors
- 2013
-
Ingår i: Journal of enzyme inhibition and medicinal chemistry (Print). - : Informa UK Limited. - 1475-6366 .- 1475-6374. ; 28:1, s. 78-88
-
Tidskriftsartikel (refereegranskat)abstract
- In this study, eight non-natural peptides and peptoids incorporating the pentacycloundecane (PCU) lactam were designed and synthesized as potential inhibitors of the wild type C-SA HIV-protease. Five of these inhibitors gave IC50 values ranging from 0.5 up to 0.75 mu M against the resistance-prone wild type C-South African HIV-protease. NMR EASY-ROESY studies enabled us to describe the secondary structure of three of these compounds in solution. The 3D structures of the selected cage peptides were also modelled in solution using QM/MM/MD simulations. Satisfactory agreement between the NMR observations and the low energy calculated structures exists. Only one of these inhibitors (11 peptoid), which showed the best IC50 (0.5 mu M), exhibited a definable 3-D structure in solution. Autodock4 and AutodockVina were used to model the potential interaction between these inhibitors and the HIV-PR. It appears that the docking results are too crude to be correlated with the relative narrow range of experimental IC50 values (0.5-10 mu M). The PCU-peptides and peptoides were several orders less toxic (145 mu M for 11 and 102 mu M for 11 peptoid) to human MT-4 cells than lopinavir (0.025 mu M). This is the first example of a polycyclic cage framework to be employed as an HIV-PR transition state analogue inhibitor and can potentially be utilized for other diseases related proteases.
|
|
| 11. |
- Makatini, Maya M., et al.
(författare)
-
Synthesis and structural studies of pentacycloundecane-based HIV-1 PR inhibitors : A hybrid 2D NMR and docking/QM/MM/MD approach
- 2011
-
Ingår i: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234 .- 1768-3254. ; 46:9, s. 3976-3985
-
Tidskriftsartikel (refereegranskat)abstract
- Pentacycloundecane (PCU) lactam-peptide based HIV protease inhibitors were synthesized and nanomolar activity against the resistance-prone wild type C-South African HIV protease is reported. NMR investigations indicated that the activity is related to the chirality of the PCU moiety and its ability to induce conformations of the coupled peptide side chain. EASY-ROESY NMR experiments gave information about the 3D structure of the cage peptides and 3D solution structure could be linked to the experimental IC(50) activity profile of the considered inhibitors. QM/MM/MD simulations of the inhibitors in solution confirmed the NMR observed conformations. Docking experiments and QM/MM/MD simulations of the inhibitor-HIV PR complexes were also performed. These computational results complimented the experimental inhibition activities and enabled us to report a unique binding mode for PCU-based inhibitors at the active site of HIV-protease enzyme. A conserved hydrogen bonding pattern between the norstatine type functional group of the PCU hydroxylactam and active site residues, ASP25/ASP25', was observed in all active compounds. The biological significance and possible mode of inhibition by PCU-based HIV PR inhibitors discussed herein provide us with a deeper understanding of the mode of action of these novel inhibitors. The PCU-peptides are between 6000 and 8500 time less toxic to human MT-4 cells than Lopinavir. This potentially creates new application avenues for these putative inhibitors to be investigated against a vast number of other disease-related proteases.
|
|
| 12. |
- Makatini, Maya M., et al.
(författare)
-
Synthesis, screening and computational investigation of pentacycloundecane-peptoids as potent CSA-HIV PR inhibitors
- 2012
-
Ingår i: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234 .- 1768-3254. ; 57, s. 459-467
-
Tidskriftsartikel (refereegranskat)abstract
- Herein, we present the first pentacycloundecane (PCU) diol peptoid derived HIV protease inhibitors with IC50 values ranging from 6.5 to 0.075 mu M. Five derivatives were synthesized in an attempt to understand the structure activity relationship of this class of compounds for HIV protease inhibition. NMR spectroscopy (new Efficient Adiabatic Symmetrized Rotating Overhauser Effect Spectroscopy, EASY-ROESY) was employed to determine the predominant conformation of the active compound. In this study docking studies and MD simulations provided insight into the binding theme of this class of peptoid inhibitors to the CSA-HIV PR active site. Conserved and stable hydrogen bonding between the hydroxyl groups of the inhibitors and the active site Asp25/Asp25' residues were observed from the docking and along the MD trajectories.
|
|
| 13. |
- Struksnes, Solveig, et al.
(författare)
-
Nurses’ conceptions of how an alternative supervision model influences their competence in assessment of nursing students in clinical practice
- 2012
-
Ingår i: Nurse Education in Practice. - Kidlington : Churchill Livingstone. - 1471-5953 .- 1873-5223. ; 12:2, s. 83-88
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: The aim of the study was to describe variations in clinical nurses' conceptions of how an alternative supervision model influences their competence in assessing nursing students in clinical practice. Background: Nursing education programme in Norway includes 50 weeks of clinical studies. Due to changes in the education system and increased focus on evidence-based practice, alternative models of supervision and assessment have been developed. Method: The study has a qualitative and descriptive design using a phenomenographic approach. Informants were 49 clinical nurses from five different nursing homes. Results: The clinical nurses' experiences are described through three description categories: 'pressure', 'encouragement' and 'development'. The informants experienced demands from the University College and colleagues, but personal and professional development was encouraged through group supervision and written information from the University College. Conclusions: The alternative supervision model supported the clinical nurses in the assessment of the nursing students, and their role as educators. The alternative supervision model also seems to strengthen the relationship between field of practice and University College.
|
|
| 14. |
|
|
