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(Gln22)-Amyloid β-Protein (1-40)

* Please kindly note that our products are not to be used for therapeutic purposes and cannot be sold to patients.

(Gln22)-Amyloid β-Protein (1-40) is a Dutch mutation (E22Q) of amyloid β-peptide that aggregates more readily than the wild-type peptide, and the resulting fibrils show increased neurotoxicity. At the concentration of 25 μm, the mutant peptide E22Q could induce apoptosis of brain endothelial cells, but WT Aβ 1-40 and the Italian mutant E22K had no significant effect on apoptosis.

Category

Functional Peptides

Catalog number

BAT-015287

CAS number

144410-00-4

Molecular Formula

C194H296N54O57S

Molecular Weight

4328.82

Specification
Reference Reading

IUPAC Name

(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-[[(2S)-5-amino-1-[[(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]-1,5-dioxopentan-2-yl]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-5-yl)-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-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-5-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

Synonyms

Amyloid β-Protein (1-40) E22Q; H-Asp-Ala-Glu-Phe-Arg-His-Asp-Ser-Gly-Tyr-Glu-Val-His-His-Gln-Lys-Leu-Val-Phe-Phe-Ala-Gln-Asp-Val-Gly-Ser-Asn-Lys-Gly-Ala-Ile-Ile-Gly-Leu-Met-Val-Gly-Gly-Val-Val-OH; L-alpha-aspartyl-L-alanyl-L-alpha-glutamyl-L-phenylalanyl-L-arginyl-L-histidyl-L-alpha-aspartyl-L-seryl-glycyl-L-tyrosyl-L-alpha-glutamyl-L-valyl-L-histidyl-L-histidyl-L-glutaminyl-L-lysyl-L-leucyl-L-valyl-L-phenylalanyl-L-phenylalanyl-L-alanyl-L-glutaminyl-L-alpha-aspartyl-L-valyl-glycyl-L-seryl-L-asparagyl-L-lysyl-glycyl-L-alanyl-L-isoleucyl-L-isoleucyl-glycyl-L-leucyl-L-methionyl-L-valyl-glycyl-glycyl-L-valyl-L-valine

Appearance

White Lyophilized Powder

Purity

≥95% by HPLC

Sequence

DAEFRHDSGYEVHHQKLVFFAQDVGSNKGAIIGLMVGGVV

Storage

Store at -20°C

Solubility

Soluble in Water

InChI

InChI=1S/C194H296N54O57S/c1-25-102(19)158(188(299)212-87-144(258)219-124(67-94(3)4)174(285)229-123(62-66-306-24)172(283)242-152(96(7)8)186(297)210-83-141(255)207-84-146(260)241-154(98(11)12)191(302)246-157(101(17)18)193(304)305)248-192(303)159(103(20)26-2)247-162(273)104(21)216-142(256)85-208-164(275)116(47-36-38-63-195)224-181(292)133(77-140(200)254)235-185(296)137(90-250)221-145(259)88-211-187(298)153(97(9)10)243-184(295)135(79-151(269)270)236-169(280)119(54-58-138(198)252)222-161(272)106(23)218-173(284)127(69-107-41-30-27-31-42-107)232-177(288)129(71-109-45-34-29-35-46-109)238-189(300)156(100(15)16)245-183(294)125(68-95(5)6)230-166(277)117(48-37-39-64-196)225-168(279)120(55-59-139(199)253)227-178(289)130(73-111-80-203-91-213-111)234-180(291)132(75-113-82-205-93-215-113)239-190(301)155(99(13)14)244-171(282)122(57-61-148(263)264)228-175(286)126(72-110-50-52-114(251)53-51-110)220-143(257)86-209-165(276)136(89-249)240-182(293)134(78-150(267)268)237-179(290)131(74-112-81-204-92-214-112)233-167(278)118(49-40-65-206-194(201)202)226-176(287)128(70-108-43-32-28-33-44-108)231-170(281)121(56-60-147(261)262)223-160(271)105(22)217-163(274)115(197)76-149(265)266/h27-35,41-46,50-53,80-82,91-106,115-137,152-159,249-251H,25-26,36-40,47-49,54-79,83-90,195-197H2,1-24H3,(H2,198,252)(H2,199,253)(H2,200,254)(H,203,213)(H,204,214)(H,205,215)(H,207,255)(H,208,275)(H,209,276)(H,210,297)(H,211,298)(H,212,299)(H,216,256)(H,217,274)(H,218,284)(H,219,258)(H,220,257)(H,221,259)(H,222,272)(H,223,271)(H,224,292)(H,225,279)(H,226,287)(H,227,289)(H,228,286)(H,229,285)(H,230,277)(H,231,281)(H,232,288)(H,233,278)(H,234,291)(H,235,296)(H,236,280)(H,237,290)(H,238,300)(H,239,301)(H,240,293)(H,241,260)(H,242,283)(H,243,295)(H,244,282)(H,245,294)(H,246,302)(H,247,273)(H,248,303)(H,261,262)(H,263,264)(H,265,266)(H,267,268)(H,269,270)(H,304,305)(H4,201,202,206)/t102-,103-,104-,105-,106-,115-,116-,117-,118-,119-,120-,121-,122-,123-,124-,125-,126-,127-,128-,129-,130-,131-,132-,133-,134-,135-,136-,137-,152-,153-,154-,155-,156-,157-,158-,159-/m0/s1

InChI Key

FWSZVUJRCZNKGC-ILZZQXMPSA-N

Canonical SMILES

CCC(C)C(C(=O)NC(C(C)CC)C(=O)NCC(=O)NC(CC(C)C)C(=O)NC(CCSC)C(=O)NC(C(C)C)C(=O)NCC(=O)NCC(=O)NC(C(C)C)C(=O)NC(C(C)C)C(=O)O)NC(=O)C(C)NC(=O)CNC(=O)C(CCCCN)NC(=O)C(CC(=O)N)NC(=O)C(CO)NC(=O)CNC(=O)C(C(C)C)NC(=O)C(CC(=O)O)NC(=O)C(CCC(=O)N)NC(=O)C(C)NC(=O)C(CC1=CC=CC=C1)NC(=O)C(CC2=CC=CC=C2)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CCCCN)NC(=O)C(CCC(=O)N)NC(=O)C(CC3=CN=CN3)NC(=O)C(CC4=CN=CN4)NC(=O)C(C(C)C)NC(=O)C(CCC(=O)O)NC(=O)C(CC5=CC=C(C=C5)O)NC(=O)CNC(=O)C(CO)NC(=O)C(CC(=O)O)NC(=O)C(CC6=CN=CN6)NC(=O)C(CCCNC(=N)N)NC(=O)C(CC7=CC=CC=C7)NC(=O)C(CCC(=O)O)NC(=O)C(C)NC(=O)C(CC(=O)O)N

1. Aggregation and metal-binding properties of mutant forms of the amyloid A beta peptide of Alzheimer's disease

C H Williams, D M Walsh, A Clements, D Allsop J Neurochem . 1996 Feb;66(2):740-7. doi: 10.1046/j.1471-4159.1996.66020740.x.

The fibrillogenic properties of Alzheimer's A beta peptides corresponding to residues 1-40 of the normal human sequence and to two mutant forms containing the replacement Ala21 to Gly or Glu22 to Gln were compared. At pH 7.4 and 37 degrees C the Gln22 peptide was found to aggregate and precipitate from solution faster than the normal A beta, whereas the Gly21 peptide aggregated much more slowly. Electron microscopy showed that the aggregates all had fibrillar structures. Circular dichroism spectra of these peptides revealed that aggregation of the normal and Gln22 sequences was associated with spectral changes consistent with a transformation from random coil to beta sheet, whereas the spectrum of the Gly21 peptide remained almost unchanged during a period in which little or no aggregation occurred. When immobilised by spotting onto nitrocellulose membranes the peptides bound similar amounts of the radioisotope 65Zn2+. Of several competing metal ions, tested at 20x the concentration of Zn2+, Cu2+ displaced > 95% of the radioactivity from all three peptides and Ni2+ produced >50% displacement in each case. Some other metal ions tested caused lesser displacement, but Fe2+ and Al3+ were without effect. In a saturation binding assay, a value of 3.2 microM was obtained for the binding of Zn2+ to A beta but our data provided no evidence for a reported higher affinity site (107 nM). The results suggest that the neuropathology associated with the Gly21 mutation is not due to enhanced fibrillogenic or different metal-binding properties of the peptide and that the binding of zinc to amyloid peptides is not a specific phenomenon.

2. Amyloid beta-protein fibrillogenesis. Detection of a protofibrillar intermediate

D M Walsh, A Lomakin, M M Condron, G B Benedek, D B Teplow J Biol Chem . 1997 Aug 29;272(35):22364-72. doi: 10.1074/jbc.272.35.22364.

Fibrillogenesis of the amyloid beta-protein (Abeta) is a seminal pathogenetic event in Alzheimer's disease. Inhibiting fibrillogenesis is thus one approach toward disease therapy. Rational design of fibrillogenesis inhibitors requires elucidation of the stages and kinetics of Abeta fibrillogenesis. We report results of studies designed to examine the initial stages of Abeta oligomerization. Size exclusion chromatography, quasielastic light scattering spectroscopy, and electron microscopy were used to characterize fibrillogenesis intermediates. After dissolution in 0.1 M Tris-HCl, pH 7.4, and removal of pre-existent seeds, Abeta chromatographed almost exclusively as a single peak. The molecules composing the peak had average hydrodynamic radii of 1.8 +/- 0.2 nm, consistent with the predicted size of dimeric Abeta. Over time, an additional peak, with a molecular weight >100,000, appeared. This peak contained predominantly curved fibrils, 6-8 nm in diameter and <200 nm in length, which we have termed "protofibrils." The kinetics of protofibril formation and disappearance are consistent with protofibrils being intermediates in the evolution of amyloid fibers. Protofibrils appeared during the polymerization of Abeta-(1-40), Abeta-(1-42), and Abeta-(1-40)-Gln22, peptides associated with both sporadic and inherited forms of Alzheimer's disease, suggesting that protofibril formation may be a general phenomenon in Abeta fibrillogenesis. If so, protofibrils could be attractive targets for fibrillogenesis inhibitors.

3. Toxicity of various amyloid beta peptide species in cultured human blood-brain barrier endothelial cells: increased toxicity of dutch-type mutant

P B Eisenhauer, T A Davies, J M Wells, R J Johnson, R E Fine J Neurosci Res . 2000 Jun 15;60(6):804-10. doi: 10.1002/1097-4547(20000615)60:63.0.CO;2-1.

The amyloid beta peptide (A beta) is the major component of the neuritic and cerebrovascular amyloid plaques that are one of the characteristic features of Alzheimer's disease (AD). This peptide has been shown to be toxic to several relevant cell types, including neurons, cerebrovascular smooth muscle cells, and endothelial cells. We have studied the toxic effects of both soluble and aggregated species of A beta(1-40) and the mutation A beta(1-40)Glu-->Gln(22), which is the major species deposited in the cerebrovascular blood vessels of victims of hereditary cerebral hemorrhage with amyloidosis, Dutch type. We find that aggregates of both peptides, as well as of A beta(1-42) and A beta(25-35), are toxic to cultured human cerebrovascular endothelial cells (hBEC) obtained from the brain of a victim of AD (at doses lower than those that are toxic to CNS neurons or leptomeningeal smooth muscle cells). Soluble A beta(1-40) Gln(22) is equally toxic to hBEC, whereas wild-type A beta(1-40) is toxic only at higher doses. This toxicity is seen at the lowest dose of A beta(1-40) Gln (22) used, 20 nM. The soluble A beta(1-40)Gln(22) aggregates on the surface of the cells, in contrast to A beta(1-40), and its toxicity can be blocked both by an inhibitor of free radical formation and by Congo red, which inhibits amyloid fibril formation. We discuss the possibility that the enhanced toxicity of A beta(1-40)Gln(22) is mediated by a A beta receptor on the endothelial cells.