The unstable dithiocarboxylic acids dithioacetic acid, 2-methyl-dithiopropionic acid, 2,2-dimethyl-dithiopropionic acid and dithiobenzoic acid were synthesized and characterized by NMR spectroscopy and GC/MS. The stable dithiocarboxylic acids 2,4,6-trimethyl benzoic acid, 2,4,6-tri-iso-propylbenzoic acid and 2,6-dimesityl benzoic acid were synthesized, isolated and characterized by spectroscopic methods and in parts by mass spectrometry and X-ray crystallography. The new data were used to re-evaluate literature data on the synthesis, spectroscopy and structural data of dithiocarboxylic acids as a fundamental class of organic compounds in general.

Misfolding and aggregation of amyloid b1-42 peptide( A b1-42) play ac entral role in the pathogenesis of Alzheimer's disease (AD). Ta rgeting the highly cytotoxic oligomeric species formed during the early stages of the aggregation process represents ap romising therapeutic strategy to reduce the toxicity associated with Ab1-42. Currently,t he thioflavin T( ThT) assay is the only established spectrofluorometric methodt os creen aggregation inhibitors. The successo ft he ThT assay is that it can detect Ab1-42 aggregates with high b-sheet content,s uch as protofibrils or fibrils, which appear in the late aggregation steps. Unfortunately,b yu sing the ThT assay,t he detection of inhibitors of early soluble oligomers that present al ow b-sheet character is challenging. Herein, an ew,f acile, and robust boron-dipyrromethene( BODIPY) real-time assay suitable for 96-well plate format, which allows screening of compounds as selectivei nhibitors of the formation of Ab1-42 oligomers, is reported.T hese inhibitors decrease the cellular toxicityo fA b1-42, although they fail in the ThT assay.T he findings have been confirmed and validated by structural analysis and cell viability assays under comparable experimental conditions. It is demonstrated that the BODIPY assay is ac onvenient methodt o screen and discover new candidate compoundst hat slow down or stop the pathological earlyo ligomerization process and are active in the cellular assay.T herefore, it is as uitable complementary screening method of the current ThT assay.Alzheimer's disease (AD) is ad evastating neurodegenerative disease that leads to progressive cognitive decline, functional impairment, and loss of independence. [1] The number of people worldwide suffering from AD is expected to reach 75 million by 2030, [2] butn oc ausative treatment exists for AD.The search for small molecules that inhibitt he aggregation of the 42-residue amyloid b protein fragment (Ab1-42; Figure 1A) is still ongoing to find at herapy for AD. Ab1-42 spontaneously self-associates into soluble oligomers and insolublea ggregates, such as protofibrilsa nd fibrils with high b-sheetc ontent.I th as been recognized that small and soluble Ab1-42 oligomers are particularly cytotoxic. [3][4][5][6][7] Thus, therapeutics trategies that intervene in the early oligomerization process, rather than in the later fibril formation step, have recently attracted attention. [8] However,d espite its therapeutic significance,t he screening of potentiali nhibitors of the early oligomerization process is still challenging. The thioflavin T( ThT) fluorescencea ssayi su sed routinelytodetermine the influence of compounds on amyloid aggregation kinetics. [9,10] However,T hT only exhibits as ubstantial fluorescencei ncreaseu pon binding to b-sheet-rich amyloid protofilaments and fibrils, but has low sensitivity to soluble early-stage oligomers. [11][12][13][14] Molecules that do not show any apparenti nhibition of amyloid aggregation,a ccording to the ThT assay,a re usually not considered for any subsequentt est...

In peptidotriazolamers every second peptide bond is replaced by a 1H-1,2,3-triazole. Such foldamers are expected to bridge the gap in molecular weight between small-molecule drugs and protein-based drugs. Amyloid β (Aβ) aggregates play an important role in Alzheimer's disease. We studied the impact of amide bond replacements by 1,4-disubstituted 1H-1,2,3-triazoles on the inhibitory activity of the aggregation "hot spots" K 16 LVFF 20 and G 39 VVIA 42 in Aβ(1-42). We found that peptido-triazolamers act as modulators of the Aβ(1-42) oligomerization. Some peptidotriazolamers are able to interfere with the formation of toxic early Aβ oligomers, depending on the position of the triazoles, which is also supported by computational studies. Preliminary in vitro results demonstrate that a highly active peptidotriazolamer is also able to cross the bloodbrain-barrier.