[Pyr11]-beta-Amyloid (11-40)

Product Name: [Pyr11]-beta-Amyloid (11-40)

Sequence One Letter Code: Pyr-VHHQKLVFFAEDVGSNKGAIIGLMVGGVV

Sequence Three Letter Code: Pyr-Val-Phe-Phe-Ala-Glu-Asp-Val-Gly-Ser-Asn Lys-Gly-Ala-Ile-Ile-Gly-Leu-Met-Val-Gly-Gly-Val-Val-OH

Cas No: 192377-94-9

Chemical Formula:C143H226N38O39S

Molecular Weight: 3133,7

Purity: 95%

Form: Lyophilized

Storage Conditions: - 20 °C

Research Area: Alzheimer's Disease

SMILES: CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)O)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC3=CNC=N3)NC(=O)[C@H](CC4=CNC=N4)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]5CCC(=O)N5

IUPAC: (4S)-5-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-6-amino-1-[[2-[[(2S)-1-[[(2S,3S)-1-[[(2S,3S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[2-[[(2S)-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-1-oxohexan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-3-(1H-imidazol-4-yl)-2-[[(2S)-3-(1H-imidazol-4-yl)-2-[[(2S)-3-methyl-2-[[(2S)-5-oxopyrrolidine-2-carbonyl]amino]butanoyl]amino]propanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]-3-methylbutanoyl]amino]-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]propanoyl]amino]-5-oxopentanoic acid

INCHIKEY: CIXXUMLEJRQLQZ-JUNKFJHTSA-N

INCHI:

InChI=1S/C143H226N38O39S/c1-24-78(19)117(138(214)154-65-106(188)160-92(52-70(3)4)128(204)166-91(48-51-221-23)126(202)175-111(72(7)8)136(212)152-62-104(186)150-63-108(190)174-113(74(11)12)141(217)179-116(77(17)18)143(219)220)181-142(218)118(79(20)25-2)180-120(196)80(21)157-105(187)64-151-121(197)86(40-32-34-49-144)163-132(208)98(58-102(147)184)170-135(211)100(67-182)161-107(189)66-153-137(213)112(73(9)10)176-134(210)99(59-110(193)194)171-124(200)90(44-47-109(191)192)162-119(195)81(22)158-127(203)94(54-82-36-28-26-29-37-82)168-129(205)95(55-83-38-30-27-31-39-83)172-139(215)115(76(15)16)178-133(209)93(53-71(5)6)167-122(198)87(41-33-35-50-145)164-123(199)89(42-45-101(146)183)165-130(206)96(56-84-60-148-68-155-84)169-131(207)97(57-85-61-149-69-156-85)173-140(216)114(75(13)14)177-125(201)88-43-46-103(185)159-88/h26-31,36-39,60-61,68-81,86-100,111-118,182H,24-25,32-35,40-59,62-67,144-145H2,1-23H3,(H2,146,183)(H2,147,184)(H,148,155)(H,149,156)(H,150,186)(H,151,197)(H,152,212)(H,153,213)(H,154,214)(H,157,187)(H,158,203)(H,159,185)(H,160,188)(H,161,189)(H,162,195)(H,163,208)(H,164,199)(H,165,206)(H,166,204)(H,167,198)(H,168,205)(H,169,207)(H,170,211)(H,171,200)(H,172,215)(H,173,216)(H,174,190)(H,175,202)(H,176,210)(H,177,201)(H,178,209)(H,179,217)(H,180,196)(H,181,218)(H,191,192)(H,193,194)(H,219,220)/t78-,79-,80-,81-,86-,87-,88-,89-,90-,91-,92-,93-,94-,95-,96-,97-,98-,99-,100-,111-,112-,113-,114-,115-,116-,117-,118-/m0/s1

Source / Species: human

Conjugation: Unconjugated

Code Nacres: NA.26

Application: [Pyr¹¹]-β-Amyloid (11–40) is a pyroglutamate-modified, N-terminally truncated amyloid-β peptide implicated in Alzheimer’s disease pathology. In this variant, glutamate at position 11 undergoes cyclization to form pyroglutamate, enhancing resistance to proteolytic degradation and increasing hydrophobicity. Pyroglutamate Aβ species are prominent components of senile plaques and are associated with accelerated aggregation and elevated neurotoxicity compared with full-length peptides. The modification promotes rapid fibril formation and stabilizes oligomeric intermediates implicated in neuronal dysfunction. [Pyr¹¹]-β-Amyloid (11–40) is widely used to investigate aggregation kinetics, plaque maturation processes, and toxicity mechanisms in cellular and biochemical models. It also supports studies examining enzymatic pathways responsible for Aβ truncation and post-translational modification. This peptide provides a valuable tool for understanding amyloid heterogeneity and evaluating therapeutic strategies targeting pathogenic Aβ variants in Alzheimer’s disease research.

Current Research: [Pyr¹¹]-β-Amyloid (11–40) is a pyroglutamate-modified, N-terminally truncated amyloid-β (Aβ) peptide increasingly recognized for its pathological relevance in Alzheimer’s disease (AD). In this variant, the glutamate residue at position 11 undergoes intramolecular cyclization to form pyroglutamate (pGlu), a post-translational modification that substantially alters the peptide’s biochemical and biophysical properties. This structural conversion enhances resistance to aminopeptidase-mediated degradation, increases hydrophobicity, and promotes conformational stability, all of which contribute to its persistence and pathogenic potential in the brain. Pyroglutamate-modified Aβ species are consistently detected in senile plaques and are considered major contributors to amyloid heterogeneity in AD pathology. Compared with full-length Aβ1–40, [Pyr¹¹]-Aβ(11–40) exhibits accelerated aggregation kinetics and an increased propensity to form β-sheet–rich fibrils. The pyroglutamate modification reduces overall charge at the N-terminus and enhances intermolecular interactions, facilitating rapid nucleation and fibril elongation. Importantly, this modified peptide also stabilizes soluble oligomeric intermediates, which are widely implicated as key mediators of synaptic dysfunction and neuronal toxicity. Current research highlights that truncated and post-translationally modified Aβ variants may act as aggregation “seeds,” accelerating the deposition of other Aβ isoforms. In vitro studies demonstrate that pyroglutamate Aβ can initiate or amplify fibrillogenesis of full-length peptides, suggesting a catalytic role in plaque maturation. This seeding capacity reinforces the concept that AD pathology involves complex interactions among multiple Aβ species rather than a single dominant isoform. Biophysical investigations of [Pyr¹¹]-β-Amyloid (11–40) commonly employ circular dichroism spectroscopy, thioflavin-based fluorescence assays, electron microscopy, and nuclear magnetic resonance techniques to characterize conformational transitions and fibril morphology. These studies reveal rapid conversion from soluble monomers to structured aggregates and demonstrate increased fibril stability relative to non-modified counterparts. Such analyses provide insight into how N-terminal cyclization influences secondary structure formation, intermolecular packing, and aggregate resilience. In cellular models, pyroglutamate-modified Aβ peptides display enhanced neurotoxicity compared with corresponding full-length variants. Exposure to [Pyr¹¹]-Aβ(11–40) has been associated with increased oxidative stress, mitochondrial dysfunction, calcium dysregulation, and activation of pro-apoptotic pathways. These findings support the hypothesis that pyroglutamate Aβ species contribute disproportionately to neuronal damage and cognitive decline. Beyond aggregation and toxicity studies, this peptide is also used to investigate enzymatic pathways responsible for Aβ truncation and modification. The formation of pyroglutamate Aβ involves sequential proteolytic processing and enzymatic cyclization, processes mediated in part by glutaminyl cyclase. Understanding these pathways is critical for identifying potential intervention points aimed at reducing pathogenic Aβ accumulation. Inhibitors of enzymes involved in truncation or cyclization are under evaluation as potential therapeutic strategies. Therapeutic research increasingly recognizes the importance of targeting modified Aβ species specifically. Antibody-based approaches and small-molecule inhibitors designed to neutralize or prevent aggregation of pyroglutamate Aβ require well-characterized model peptides for validation. [Pyr¹¹]-β-Amyloid (11–40) provides a defined system for assessing binding specificity, aggregation inhibition, and toxicity attenuation under controlled experimental conditions. Overall, [Pyr¹¹]-β-Amyloid (11–40) represents a highly relevant model for studying the biochemical diversity and pathogenic complexity of amyloid-β in Alzheimer’s disease. Its enhanced aggregation propensity, stability, and neurotoxic potential make it an essential tool for investigating plaque formation, oligomer dynamics, and therapeutic targeting strategies. By enabling focused analysis of a disease-associated Aβ variant, this peptide advances understanding of amyloid heterogeneity and its contribution to neurodegeneration.