Conformation of Pyroglutamated Amyloid β (3-40) and (11-40) Fibrils - Extended or Hairpin?

Amyloid β (Aβ) is a hallmark protein of Alzheimer's disease. One physiologically important Aβ variant is formed by initial N-terminal truncation at a glutamic acid position (either E or E), which is subsequently cyclized to a pyroglutamate (either pE or pE). Both forms have been found in high concentrations in the core of amyloid plaques and are likely of high importance in the pathology of Alzheimer's disease.

Exploring the potential of tamoxifen-based copper(ii) dichloride in breast cancer therapy.

For decades, tamoxifen-based hormone therapy has effectively addressed oestrogen receptor positive (ER+) luminal A breast cancer. Nonetheless, the emergence of tamoxifen resistance required innovative approaches, leading to hybrid metallodrugs with several therapeutic effects besides the inhibition of oestrogen receptor α (ERα). Drawing inspiration from tamoxifen metabolite structures (4-hydroxytamoxifen and 4,4'-dihyroxytamoxifen), a phenyl ring was replaced by a bidentate 2,2'-bipyridine donor moiety to give 4-[1,1-bis(4-methoxyphenyl)but-1-en-2-yl]-2,2'-bipyridine (L), enabling coordination of bioactive transition metal compounds such as copper(ii) dichloride, yielding [CuCl(μ-Cl)(L-κ,')] (1).

Correction: Kazimir et al. Metallodrugs against Breast Cancer: Combining the Tamoxifen Vector with Platinum(II) and Palladium(II) Complexes. 2023, , 682.

In the original publication [...

Metallodrugs against Breast Cancer: Combining the Tamoxifen Vector with Platinum(II) and Palladium(II) Complexes.

The luminal A-subtype of breast cancer, where the oestrogen receptor α (ERα) is overexpressed, is the most frequent one. The prodrug tamoxifen () is the clinically used agent, inhibiting the ERα activity via the formation of several active metabolites, such as 4-hydroxytamoxifen () or 4,4'-dihydroxytamoxifen (). In this study, we present the tamoxifen derivative 4-[1,1-bis(4-methoxyphenyl)but-1-en-2-yl]-2,2'-bipyridine (), which was combined with platinum or palladium dichloride, the former a well-known scaffold in anticancer treatment, to give [PtCl(-κ,')] () or [PdCl(-κ,'] ().

How Single Site Mutations Can Help Understanding Structure Formation of Amyloid β.

Amyloid fibrils represent the structural endpoint on the energetic (mis)folding landscape of very many proteins. Physiologically, amyloid fibrils are observed as a characteristic hallmark in misfolding diseases often associated with degenerative and neurodegenerative disorders. In the beginning of the scientific discussion, the focus is laid on the fibrillar state, but over the time it becomes increasingly clear that low molecular weight and transient aggregates are of crucial importance for pathological mechanisms.