[Gly22]-beta-Amyloid (1-40), Arctic Mutation

Product Name: [Gly22]-beta-Amyloid (1-40), Arctic Mutation

Sequence One Letter Code: DAEFRHDSGYEVHHQKLVFFAGDVGSNKGAIIGLMVGGVV

Sequence Three Letter Code: H-Asp-Ala-Glu-Phe-Arg-His-Asp-Ser-Gly-Tyr-Glu-Val-His-His-Gln-Lys-Leu-Val-Phe-Phe-Ala-Gly-Asp-Val-Gly-Ser-Asn-Lys-Gly-Ala-Ile-Ile-Gly-Leu-Met-Val-Gly-Gly-Val-Val-OH

Cas No: 175010-18-1

Chemical Formula:C191H291N53O56S

Molecular Weight: 4258.1

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)CNC(=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](CCC(=O)O)NC(=O)[C@H](CC5=CC=C(C=C5)O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC6=CNC=N6)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC7=CC=CC=C7)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)N

IUPAC: (4S)-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(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]-2-oxoethyl]amino]-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-amino-3-carboxypropanoyl]amino]propanoyl]amino]-5-oxopentanoic acid

INCHIKEY: HREHWFHVRHRTCT-FEPTUWFISA-N

INCHI:

InChI=1S/C191H291N53O56S/c1-25-101(19)156(185(294)209-86-142(254)216-122(65-93(3)4)171(280)226-121(60-64-301-24)169(278)238-150(95(7)8)183(292)207-81-138(250)203-82-144(256)237-152(97(11)12)188(297)242-155(100(17)18)190(299)300)244-189(298)157(102(20)26-2)243-160(269)104(22)213-139(251)83-205-162(271)115(47-36-38-61-192)221-178(287)131(75-137(196)249)232-182(291)135(89-246)219-143(255)87-208-184(293)151(96(9)10)239-181(290)132(76-148(263)264)218-140(252)84-204-158(267)103(21)215-170(279)125(67-106-41-30-27-31-42-106)229-174(283)127(69-108-45-34-29-35-46-108)234-186(295)154(99(15)16)241-180(289)123(66-94(5)6)227-164(273)116(48-37-39-62-193)222-166(275)118(54-57-136(195)248)224-175(284)128(71-110-78-199-90-210-110)231-177(286)130(73-112-80-201-92-212-112)235-187(296)153(98(13)14)240-168(277)120(56-59-146(259)260)225-172(281)124(70-109-50-52-113(247)53-51-109)217-141(253)85-206-163(272)134(88-245)236-179(288)133(77-149(265)266)233-176(285)129(72-111-79-200-91-211-111)230-165(274)117(49-40-63-202-191(197)198)223-173(282)126(68-107-43-32-28-33-44-107)228-167(276)119(55-58-145(257)258)220-159(268)105(23)214-161(270)114(194)74-147(261)262/h27-35,41-46,50-53,78-80,90-105,114-135,150-157,245-247H,25-26,36-40,47-49,54-77,81-89,192-194H2,1-24H3,(H2,195,248)(H2,196,249)(H,199,210)(H,200,211)(H,201,212)(H,203,250)(H,204,267)(H,205,271)(H,206,272)(H,207,292)(H,208,293)(H,209,294)(H,213,251)(H,214,270)(H,215,279)(H,216,254)(H,217,253)(H,218,252)(H,219,255)(H,220,268)(H,221,287)(H,222,275)(H,223,282)(H,224,284)(H,225,281)(H,226,280)(H,227,273)(H,228,276)(H,229,283)(H,230,274)(H,231,286)(H,232,291)(H,233,285)(H,234,295)(H,235,296)(H,236,288)(H,237,256)(H,238,278)(H,239,290)(H,240,277)(H,241,289)(H,242,297)(H,243,269)(H,244,298)(H,257,258)(H,259,260)(H,261,262)(H,263,264)(H,265,266)(H,299,300)(H4,197,198,202)/t101-,102-,103-,104-,105-,114-,115-,116-,117-,118-,119-,120-,121-,122-,123-,124-,125-,126-,127-,128-,129-,130-,131-,132-,133-,134-,135-,150-,151-,152-,153-,154-,155-,156-,157-/m0/s1

Source / Species: human

Conjugation: Unconjugated

Code Nacres: NA.26

Application: [Gly22]-β-Amyloid (1–40), Arctic mutation is a synthetic peptide corresponding to the Aβ(1–40) sequence containing the familial Alzheimer’s disease–associated E22G substitution. This mutation enhances aggregation propensity and promotes formation of soluble protofibrils, which are considered highly neurotoxic species. The Arctic variant is linked to early-onset Alzheimer’s disease and is widely used to study aggregation kinetics, structural transitions, and protofibril-mediated toxicity. This peptide supports mechanistic investigations into amyloid assembly pathways, synaptic dysfunction, and disease-related conformational changes. It is also suitable for screening aggregation inhibitors and evaluating therapeutic strategies targeting amyloid-driven neurodegeneration.

Current Research: [Gly22]-β-Amyloid (1–40), Arctic mutation is a synthetic peptide corresponding to the human amyloid-β (Aβ) 1–40 sequence containing the familial Alzheimer’s disease (FAD)–associated E22G substitution in the central hydrophilic region. This mutation, commonly referred to as the “Arctic” mutation, was identified in patients with early-onset Alzheimer’s disease and is characterized by enhanced amyloid aggregation and increased formation of soluble protofibrillar assemblies. Residue 22 lies within the critical 21–23 segment of Aβ, a region that strongly influences intermolecular interactions and β-sheet formation. Substitution of glutamic acid with glycine removes a negatively charged side chain, reducing electrostatic repulsion and altering local conformational dynamics. This seemingly subtle change significantly accelerates nucleation-dependent aggregation kinetics and favors the formation of oligomeric and protofibrillar intermediates over monomeric or fully mature fibrillar species. Biophysically, the Arctic variant demonstrates increased aggregation propensity compared to wild-type Aβ(1–40). In vitro studies show shortened lag phases in Thioflavin T fluorescence assays, enhanced β-sheet content as assessed by circular dichroism spectroscopy, and rapid formation of soluble protofibrils detectable by size-exclusion chromatography and electron microscopy. These protofibrillar species are widely regarded as highly neurotoxic intermediates, contributing to synaptic dysfunction and neuronal impairment. Mechanistically, soluble oligomers and protofibrils derived from the Arctic mutation are implicated in disruption of synaptic signaling. Experimental models indicate that these assemblies interfere with long-term potentiation (LTP), alter dendritic spine morphology, and impair neurotransmitter receptor trafficking. The increased stability and persistence of protofibrils in the Arctic variant make it a particularly valuable model for studying early toxic events preceding plaque deposition. The Arctic mutation also provides insight into conformational transitions within amyloid assembly pathways. Structural analyses using NMR spectroscopy, cryo-electron microscopy, and computational modeling have been employed to compare wild-type and E22G variants. These studies highlight differences in β-sheet packing, fibril polymorphism, and intermolecular contact patterns. Such comparisons help elucidate how single-residue substitutions influence aggregation landscapes and disease phenotype severity. In cellular systems, [Gly22]-Aβ(1–40) is used to investigate oxidative stress induction, mitochondrial dysfunction, calcium dysregulation, and apoptotic signaling. Neuronal cultures exposed to Arctic Aβ oligomers exhibit enhanced cytotoxic responses relative to wild-type peptide, reinforcing the pathogenic significance of protofibrillar assemblies. These properties make the peptide particularly suitable for dissecting mechanisms of amyloid-induced neurotoxicity. In therapeutic research, the Arctic variant serves as a stringent model for screening aggregation inhibitors, conformation-specific antibodies, small-molecule stabilizers, and protofibril-targeting compounds. Because it preferentially forms soluble toxic intermediates, it is well suited for evaluating strategies aimed at preventing early oligomer formation rather than simply reducing mature fibril deposition. Additionally, it is used in studies examining antibody selectivity for protofibrillar versus fibrillar Aβ species. Overall, [Gly22]-β-Amyloid (1–40), Arctic mutation is a disease-relevant amyloid variant with enhanced aggregation kinetics and protofibril formation capacity. Its strong association with early-onset familial Alzheimer’s disease and its propensity to generate neurotoxic soluble assemblies make it an essential tool for mechanistic studies of amyloid assembly, synaptic dysfunction, and therapeutic intervention targeting amyloid-driven neurodegeneration.