Peptides

KKLVFFA contains the KLVFF sequence, which is the minimum sequence binding the full-length amyloid β-protein. It showed improved water solubility compared with KLVFF (H-3682). It can be used as a labeled probe for screening defined sequences in the full-length amyloid β-protein.

The Italian mutation of β-amyloid 1-40 (E22K) aggregates more rapidly than the wild-type sequence 1-40. It showed increased neurotoxicity, which (according to a solid-phase NMR-study of Masuda et al.) may be due to the salt bridge formed between Lys²² and Asp²³ in the minor conformer. As the Arctic, Flemish, and Dutch mutants, the Italian mutant is degraded considerably more slowly than wild-type Aβ by neprilysin.

The Italian mutation (E22K) aggregates more rapidly than the wild-type sequence.

Oxidation of Met35 attenuates the formation of Aβ40 oligomers.

(Met(O)³?)-Amyloid β-protein (1-42) (H-5888), in contrast to Aβ 1-42 (H-1368), has been shown to be non-toxic to 9-11 day-old rat embryonic hippocampal neuronal cultures and not to produce any protein oxidation. It has also been demonstrated that fibril formation is not affected by Met(O)³?. For the Nle analog see H-7308.

Sulfoxide of Aβ 25-35.

Maiti et al. could show that, in contrast to the sulfoxide of Aβ (1-42), the sulfone was as toxic and aggregated as fast as wild-type Aβ (1-42).

The reactive thioether of Met³? is crucial for the activity of Aβ 1-40 and Aβ 1-42. Due to the replacement of Met by inert Nle, M35Nle Aβ 1-40 was no longer toxic to cultured hippocampal neurons and had little effect on the level of protein carbonyl residues. The Nle peptide showed the same propensity to aggregate, whereas sulfoxide formation hindered the required conformational transition from random coil to β-sheet.

The thioether of Met³? plays a critical role in the oxidative stress induced by Aβ 1-42 and its neurotoxicity. The norleucine analog Aβ 1-42 M35Nle forms fibrils morphologically indistinguishable from the ones of the native sequence though lacking their neurotoxicity.

pEVHHQKLVFFAEDVGSNKGAIIGLMVGGVV, the N-terminally truncated isoform of the amyloid β-protein (Aβ) beginning with a pyroglutamate (Pyr) residue at position 11 was used in experiments studying the generality of fibrillogenesis-related helix formation. Comparing the fibrillogenesis kinetics of many of the most important clinically relevant amyloid β-protein alloforms it could be observed that among these peptides (Pyr¹¹)-amyloid β-protein (11-40) exhibited the greatest retardation of fibrillization rate.

The pyroglutamate-modified amyloid-β peptides derived from Aβ40 (H-7422) and Aβ42 (H-4796) have gained considerable attention as potential key participants in the pathology of Alzheimer's disease (AD) due to their abundance in AD brain, high aggregation propensity, stability, and cellular toxicity. Aβ40 and 42 can be N-terminally truncated by action of cathepsin B. The cyclization of Glu³ is catalyzed by glutaminyl cyclase. Hence, inhibition of these enzymes could be a therapeutic approach to AD.

(Pyr³)-Amyloid β-Protein (3-42) was found to be the predominant amyloid β-peptide structure deposited in human brain of Alzheimer's disease and Down's syndrome patients. Therefore, (Pyr³)-Aβ (3-42) is suggested to accumulate in the brain and to trigger the formation of insoluble amyloid β-peptide deposits. Nussbaum et al. studies the Prion-like behaviour and tau-dependent cytotoxicity of the truncated Aβ sequence.

A mutation very close to the β-secretase cleavage site of APP. The Icelandic mutation A2T of Aβ42 turned out to be less pathogenic than the native sequence. The precursor APP A673T was the first APP variant discovered in humans reducing the risk of Alzheimer's disease. A2T as well affects γ-secretase cleavage, the mutant was an inefficient substrate in a cell-based assay of the enzyme.

A mutation very close to the β-secretase cleavage site of APP (A673V). Contrary to the protective Icelandic mutation A2T, the recessive A2V mutation may increase the risk of Alzheimer's disease. Cantu et al. observed that APP A673V is associated with the early onset of AD-type dementia in homozygous individuals, whereas it has a protective effect in the heterozygous state.

Cerebral amyloid angiopathy (CAA) is a common finding in Alzheimer's disease in which amyloid-Aβ vascular deposits are featured in >80% of the cases. Mutations in the positions 21-23 (e.g. Dutch mutation E22Q) are primarily associated with CAA, although they manifest with strikingly different clinical phenotypes: cerebral hemorrhage or dementia. The Piedmont L34V Aβ mutant, located outside this hot spot, shows a similar hemorrhagic phenotype, albeit less aggressive than the widely studied Dutch variant.

5-FAM-Amyloid β；-Protein (1-40) 是 FAM 荧光标记的 β；-Amyloid (1-40) 肽（&Lambda；ex=492nm 和 &Lambda；em=518nm）。

Fluorescent dye-labeled inactive control for H-1368, H-6466, H-8146.

Anderson and Webb could verify using transmission electron microscopy that N-terminal labeling of Aβ40 with TAMRA and other fluorescent dyes does not prevent the formation of protofibrils and amyloid fibrils of various widths.

Intramolecularly quenched fluorescent substrate containing the ortho-aminobenzoyl (Abz) / N-(2,4-dinitrophenyl)ethylenediamine (EDDnp) groups as the donor / acceptor pair. It corresponds to the Swedish-mutated (JMV2236) β-amyloid precursor protein (βAPP) sequence targeted by β-secretase BACE (β-site APP-cleaving activity). This FRET substrate is more selectively cleaved by BACE1 and BACE2 than by cathepsin D, a disintegrin and metalloprotease 10 (ADAM10), tumor necrosis α-converting enzyme (TACE), presenilin-1 (PS1), or presenilin-2 (PS2).

Intramolecularly quenched fluorescent substrate containing the ortho-aminobenzoyl (Abz) / N-(2,4-dinitrophenyl)ethylenediamine (EDDnp) groups as the donor / acceptor pair. It mimicks the wild-type (JMV2235) β-amyloid precursor protein (βAPP) sequence targeted by β-secretase BACE (β-site APP-cleaving activity). This FRET substrate is cleaved by BACE1, BACE2, and cathepsin D.

A sensitive fluorogenic (FRET) substrate developed for the analysis of γ-secretase from post mortem non-Alzheimer's and Alzheimer's disease human brain isolates.