| 41. |
- Brandt, Jasmine, et al.
(författare)
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Thyroid-associated genetic polymorphisms in relation to breast cancer risk in the Malmö Diet and Cancer Study
- 2018
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 142:7, s. 1309-1321
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have suggested that thyroid function is associated with breast cancer risk, which could have an important clinical impact, as one in eight women will develop a thyroid disorder during her lifetime. However, the underlying pathomechanism behind the association is still unknown. We used the Malmö Diet and Cancer Study (a population-based prospective study consisting of 17,035 women) to examine 17 single nucleotide polymorphisms (SNPs) previously related to levels of free thyroxine (free T4) and thyroid peroxidase antibodies (TPO-Ab) as potential genetic risk factors for breast cancer. A baseline examination including free T4 and TPO-Ab levels was conducted at the time of inclusion. Genotyping was performed on 901 breast cancer patients and 3335 controls. Odds ratios (95% confidence intervals) for high free T4, TPO-Ab positivity, and breast cancer were calculated by logistic regression and adjusted for confounders. We identified one free T4-related SNP (rs2235544, D101 gene) that was significantly associated with both free T4 level and breast cancer risk. There was a suggested association between rs11675434 (TPO gene) and TPO-Ab level, and TPO-Ab-related rs11675434 (TPO), rs3094228 (HCP5), rs1033662 (no registered gene), and rs301806 (RERE) were associated with breast cancer risk. There was an indicated interaction between rs6485050 (no registered gene) and free T4 level in regards to breast cancer risk. This is the first study to suggest an association between thyroid-related SNPs and breast cancer risk. All SNPs have a biological plausibility of being associated with breast cancer risk, and may contribute to the genetic predisposition to breast cancer.
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| 42. |
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| 43. |
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| 44. |
- Brandt, Peter, et al.
(författare)
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Chromium-salen-mediated alkene epoxidation : a theoretical and experimental study indicates the importance of spin-surface crossing and the presence of a discrete intermediate.
- 2002
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Ingår i: Chemistry - A European Journal. - 0947-6539 .- 1521-3765. ; 8:18, s. 4299-307
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Tidskriftsartikel (refereegranskat)abstract
- The mechanism of alkene epoxidation by chromium(v) oxo salen complexes has been studied by DFT and experimental methods. The reaction is compared to the closely related Mn-catalyzed process in an attempt to understand the dramatic difference in selectivity between the two systems. Overall, the studies show that the reactions have many similarities, but also a few critical differences. In agreement with experiment, the chromium system requires a change from low- to high-spin in the catalytic cycle, whereas the manganese system can proceed either with spin inversion or entirely on the high-spin surface. The low-spin addition of metal oxo species to an alkene leads to an intermediate which forms epoxide either with a barrier on the low-spin surface or without a barrier after spin inversion. Supporting evidence for this intermediate was obtained by using vinylcyclopropane traps. The chromium(v) oxo complexes can adopt a stepped shape or form a more concave surface, analogous to previous results on manganese salen complexes.
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| 45. |
- Brandt, Peter, et al.
(författare)
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Deconstruction of Non-Nucleoside Reverse Transcriptase Inhibitors of Human Immunodeficiency Virus Type 1 for Exploration of the Optimization Landscape of Fragments
- 2011
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804.
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Tidskriftsartikel (refereegranskat)abstract
- This study has taken a closer look at the theoretical basis for protein-fragment interactions. The approach involved the deconstruction of 3 non-nucleoside inhibitors of HIV-1 reverse transcriptase and investigation of the interaction between 21 substructures and the enzyme. It focused on the concept of ligand efficiency and showed that ligand independent free energy fees (ΔG(ind)) are crucial for the understanding of the binding affinities of fragments. A value of 7.0 kcal mol(-1) for the ΔG(ind) term is shown to be a lower limit for the NNRTI binding pocket of HIV-1 RT. The addition of the ΔG(ind) term to the dissociation free energy in the calculation of a corrected ligand efficiency, in combination with the lack of an efficient ligand binding hot spot in the NNIBP, fully explains the existence of nonbinding NNRTI substructures. By applying the concept to a larger set of ligands, we could define a binding site profile that indicates the absence of an efficient fragment binding hot spot but an efficient binding of full-sized NNRTIs. The analysis explains some of the challenges in identifying fragments against flexible targets involving conformational changes and how fragments may be prioritized.
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| 46. |
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| 47. |
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| 48. |
- Brandt, Peter, et al.
(författare)
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Molecular Mechanics (MM3) Parameters for Ruthenium(II)-Polypyridyl Complexes.
- 1998
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Ingår i: Inorganic Chemistry. - 0020-1669 .- 1520-510X. ; 37:16, s. 4120-4127
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Tidskriftsartikel (refereegranskat)abstract
- We have developed molecular mechanics parameters for Ru(II)-polypyridyl coordination compounds with the MM3 force field in MacroModel. X-ray structures, together with a B3LYP frequency calculation on a model system, have been utilized in the parametrization. The performance of the force field and the quality of each parameter is analyzed. A clear qualitative correlation have been found between coordination geometry and emission properties for the ruthenium polypyridyl complexes examined in this paper.
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| 49. |
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| 50. |
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