Peptidomimetics That Inhibit and Partially Reverse the Aggregation of Aβ1–42

Stark, Tina; Lieblein, Tobias; Pohland, Maximilian; Kalden, Elisabeth; Freund, Petra; Zangl, René; Grewal, Rekha; Heilemann, Mike; Eckert, Gunter P.; Morgner, Nina; Göbel, Michael W.

doi:10.1021/acs.biochem.7b00223

Cited by 17Alzheimer's disease research and treatmentsChemical Synthesis and AnalysisCholinesterase and Neurodegenerative Diseases

Peptidomimetics That Inhibit and Partially Reverse the Aggregation of Aβ1–42

Stark, Tina, Lieblein, Tobias, Pohland, Maximilian, Kalden, Elisabeth, Freund, Petra, Zangl, René, Grewal, Rekha, Heilemann, Mike +3 more·2017·Biochemistry

DOI 10.1021/acs.biochem.7b00223

Open this paper in CoChat — free account

Abstract

The peptide sequence KLVFF resembles the hydrophobic core of the Aβ peptide known to form amyloid plaques in Alzheimer’s disease. Starting from its retro-inverso peptide, we have synthesized three generations of peptidomimetics. Step by step natural amino acids have been replaced by aromatic building blocks accessible from the Pd-catalyzed Catellani reaction. The final compound 18 is stable against proteolytic decay and largely prevents the aggregation of Aβ 1–42 over extended periods of time. The activity of the new inhibitors was tested first by fluorescence correlation spectroscopy. For closer examination of compound 18, additional techniques were also applied: laser-induced liquid bead ion desorption mass spectrometry, confocal laser scanning microscopy, thioflavin T fluorescence, and gel electrophoresis. Compound 18 not only retards the aggregation of chemically synthesized Aβ but also can partially dissolve the oligomeric structures. Thioflavin binding mature fibrils, however, seem to resist the inhibitor.

Integrity signals

Registry

Crossref · 10.1021/acs.biochem.7b00223

Cites

54 of 54 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

KLVFF is a peptide sequence that mimics the hydrophobic center region of Aβ and eventually replaces natural polypeptides; it is resistant to proteolytic degradation and can break down oligomerics to a limited level.
“Another promising treatment is KLVFF, a peptide sequence that mimics the hydrophobic center region of the Aβ and eventually replaces natural polypeptides. The KLVFF compound, which is resistant to proteolytic degradation and can also break down oligomerics to a limited level, is the final compound, can also break down oligomerics to a minor amount. (Stark et al., 2017).”
From An update on the novel and approved drugs for Alzheimer disease (2022) · cites this paper as Stark et al., 2017
KLVFF is a peptide sequence that resembles the hydrophobic central part of Aβ and gradually replaces natural polypeptides.
“KLVFF is a peptide sequence that resembles the hydrophobic central part of the Aβ and gradually replaces natural polypeptides.”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [51]
Peptidomimetics that inhibit and partially reverse aggregation of Aβ42 are tested in transmission electron microscopic studies.
“Nowadays, specific agents in the form of peptidomimetics that inhibit and partially reverse the aggregation of Aβ42 are tested in transmission electron microscopic studies.”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [51]
Compound 18 mainly prevents aggregation of Aβ42 and can also dissolve oligomerics to a limited extent; it is resilient in proteolytic decomposition.
“The KLVFF compound that mainly prevents the aggregation of Aβ42 and can also dissolve the oligomerics to a limited extend is the final compound 18, which is resilient in proteolytic decomposition.51”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [51]

Fiji: an open-source platform for biological-image analysis
Schindelin, J., Arganda-Carreras, I., Frise, E., Kaynig, V., Longair, M., Pietzsch, T., Preibisch, S., Rueden, C., Saalfeld, S., Schmid, B., et al. (2012) · Nature Methods · doi:10.1038/nmeth.2019 · Cited by 66,890 · see citing works
Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide
Haass, C., & Selkoe, D. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2101 · Cited by 4,744 · see citing works
Alzheimer’s disease
Blennow, K., de Leon, M. J., & Zetterberg, H. (2006) · The Lancet · doi:10.1016/s0140-6736(06)69113-7 · Cited by 3,134 · see citing works
The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease
Sevigny, J., Chiao, P., Bussière, T., Weinreb, P. H., Williams, L., Maier, M., Dunstan, R., Salloway, S., Chen, T., Ling, Y., et al. (2016) · Nature · doi:10.1038/nature19323 · Cited by 3,059 · see citing works
Aβ Oligomers – a decade of discovery
Walsh, D. M., & Selkoe, D. J. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04426.x · Cited by 1,938 · see citing works
A Common Mechanism Underlying Promiscuous Inhibitors from Virtual and High-Throughput Screening
McGovern, S. L., Caselli, E., Grigorieff, N., & Shoichet, B. K. (2002) · Journal of Medicinal Chemistry · doi:10.1021/jm010533y · Cited by 1,048 · see citing works
Inhibition of Amyloid Fibril Formation by Polyphenols: Structural Similarity and Aromatic Interactions as a Common Inhibition Mechanism
Porat, Y., Abramowitz, A., & Gazit, E. (2005) · Chemical Biology & Drug Design · doi:10.1111/j.1747-0285.2005.00318.x · Cited by 994 · see citing works
Arrest of -Amyloid Fibril Formation by a Pentapeptide Ligand
Tjernberg, L. O., Näslund, J., Lindqvist, F., Johansson, J., Karlström, A. R., Thyberg, J., Terenius, L., & Nordstedt, C. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.15.8545 · Cited by 963 · see citing works
Amyloid-β protein oligomerization and the importance of tetramers and dodecamers in the aetiology of Alzheimer's disease
Bernstein, S. L., Dupuis, N., Lazo, N. D., Wyttenbach, T., Condron, M. M., Bitan, G., Teplow, D. B., Shea, J., Ruotolo, B. T., Robinson, C. V., et al. (2009) · Nature Chemistry · doi:10.1038/nchem.247 · Cited by 918 · see citing works
The Amyloid Beta Peptide: A Chemist’s Perspective. Role in Alzheimer’s and Fibrillization
Hamley, I. W. (2012) · Chemical Reviews · doi:10.1021/cr3000994 · Cited by 881 · see citing works
β-sheet breaker peptides inhibit fibrillogenesis in a rat brain model of amyloidosis: Implications for Alzheimer's therapy
Soto, C. A., Sigurdsson, E. M., Morelli, L., Kumar, R., Castaño, E. M., & Frangione, B. (1998) · Nature Medicine · doi:10.1038/nm0798-822 · Cited by 874 · see citing works
Atomic Resolution Structure of Monomorphic Aβ42 Amyloid Fibrils
Colvin, M. T., Silvers, R., Ni, Q. Z., Can, T. V., Sergeyev, I. V., Rosay, M., Donovan, K. J., Michael, B. C., Wall, J. S., Linse, S. S., et al. (2016) · Journal of the American Chemical Society · doi:10.1021/jacs.6b05129 · Cited by 812 · see citing works
Atomic-resolution structure of a disease-relevant Aβ(1–42) amyloid fibril
Wälti, M. A., Ravotti, F., Arai, H., Glabe, C. G., Wall, J. S., Böckmann, A., Güntert, P., Meier, B. H., & Riek, R. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1600749113 · Cited by 810 · see citing works
Alzheimer's Disease: From Pathology to Therapeutic Approaches
Jakob‐Roetne, R., & Jacobsen, H. (2009) · Angewandte Chemie International Edition · doi:10.1002/anie.200802808 · Cited by 626 · see citing works
Catalytic Sequential Reactions Involving Palladacycle-Directed Aryl Coupling Steps
Catellani, M., Motti, E., & Ca’, N. D. (2008) · Accounts of Chemical Research · doi:10.1021/ar800040u · Cited by 571 · see citing works
Inhibition of Alzheimer's Amyloidosis by Peptides That Prevent β-Sheet Conformation
Soto, C. A., Kindy, M. S., Baumann, M., & Frangione, B. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.1413 · Cited by 432 · see citing works
Cyclohexanehexol inhibitors of Aβ aggregation prevent and reverse Alzheimer phenotype in a mouse model
McLaurin, J., Kierstead, M. E., Brown, M. E., Hawkes, C. A., Lambermon, M. H. L., Phinney, A. L., Darabie, A. A., Cousins, J. E., French, J. E., Lan, M. F., et al. (2006) · Nature Medicine · doi:10.1038/nm1423 · Cited by 366 · see citing works
Amyloid β-Protein: Monomer Structure and Early Aggregation States of Aβ42 and Its Pro 19 Alloform
Bernstein, S. L., Wyttenbach, T., Baumketner, A., Shea, J., Bitan, G., Teplow, D. B., & Bowers, M. T. (2005) · Journal of the American Chemical Society · doi:10.1021/ja044531p · Cited by 341 · see citing works
Lysine-Specific Molecular Tweezers Are Broad-Spectrum Inhibitors of Assembly and Toxicity of Amyloid Proteins
Sinha, S., Lopes, D. H. J., Du, Z., Pang, E. S., Shanmugam, A., Lomakin, A., Talbiersky, P., Tennstaedt, A., McDaniel, K., Bakshi, R., et al. (2011) · Journal of the American Chemical Society · doi:10.1021/ja206279b · Cited by 296 · see citing works
A facile method for expression and purification of the Alzheimer’s disease‐associated amyloid β‐peptide
Walsh, D. M., Thulin, E., Minogue, A. M., Gustavsson, N., Pang, E. S., Teplow, D. B., & Linse, S. S. (2009) · FEBS Journal · doi:10.1111/j.1742-4658.2008.06862.x · Cited by 284 · see citing works
Screening and classifying small-molecule inhibitors of amyloid formation using ion mobility spectrometry–mass spectrometry
Young, L. M., Saunders, J. C., Mahood, R. A., Revill, C., Foster, R. J., Tu, L., Raleigh, D. P., Radford, S. E., & Ashcroft, A. E. (2014) · Nature Chemistry · doi:10.1038/nchem.2129 · Cited by 281 · see citing works
Small-molecule aggregates inhibit amyloid polymerization
Feng, B. Y., Toyama, B. H., Wille, H., Colby, D. W., Collins, S. R., May, B. C. H., Prusiner, S. B., Weissman, J. S., & Shoichet, B. K. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.65 · Cited by 257 · see citing works
Inhibition of β-Amyloid(40) Fibrillogenesis and Disassembly of β-Amyloid(40) Fibrils by Short β-Amyloid Congeners ContainingN-Methyl Amino Acids at Alternate Residues
Gordon, D. J., Sciarretta, K. L., & Meredith, S. C. (2001) · Biochemistry · doi:10.1021/bi002416v · Cited by 254 · see citing works
Function and toxicity of amyloid beta and recent therapeutic interventions targeting amyloid beta in Alzheimer's disease
Rajasekhar, K., Chakrabarti, M., & Govindaraju, T. (2015) · Chemical Communications · doi:10.1039/c5cc05264e · Cited by 241 · see citing works
Small molecule inhibitors of amyloid β peptide aggregation as a potential therapeutic strategy for Alzheimer's disease
Nie, Q., Du, X., & Geng, M. (2011) · Acta Pharmacologica Sinica · doi:10.1038/aps.2011.14 · Cited by 239 · see citing works
Reduction of amyloid load and cerebral damage in transgenic mouse model of Alzheimer's disease by treatment with a β‐sheet breaker peptide
Permanne, B., Adessi, C., Saborı́o, G. P., Fraga, S., Frossard, M., Dorpe, J. V., Dewachter, I., Banks, W. A., LEUVEN, F. V., & Soto, C. A. (2002) · The FASEB Journal · doi:10.1096/fj.01-0841fje · Cited by 218 · see citing works
An anticancer drug suppresses the primary nucleation reaction that initiates the production of the toxic Aβ42 aggregates linked with Alzheimer’s disease
Habchi, J., Arosio, P., Perni, M., Costa, A. R., Yagi‐Utsumi, M., Joshi, P., Chia, S., Cohen, S. I. A., Müller, M. B. D., Linse, S. S., et al. (2016) · Science Advances · doi:10.1126/sciadv.1501244 · Cited by 201 · see citing works
Pharmacological Profiles of Peptide Drug Candidates for the Treatment of Alzheimer's Disease
Adessi, C., Frossard, M., Boissard, C., Fraga, S., Biéler, S., Rückle, T., Vilbois, F., Robinson, S. M., Mutter, M., Banks, W. A., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211976200 · Cited by 197 · see citing works
C-terminal peptides coassemble into Aβ42 oligomers and protect neurons against Aβ42-induced neurotoxicity
Fradinger, E. A., Monien, B. H., Urbanc, B., Lomakin, A., Tan, M., Li, H., Spring, S. M., Condron, M. M., Cruz, L., Xie, C.-W., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0807163105 · Cited by 186 · see citing works
Amyloid cascade in Alzheimer's disease: Recent advances in medicinal chemistry
Mohamed, T., Shakeri, A., & Rao, P. P. N. (2016) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2016.02.049 · Cited by 181 · see citing works
Designing Peptide Inhibitors for Oligomerization and Toxicity of Alzheimer's β-Amyloid Peptide
Austen, B., Paleologou, K. E., Ali, S. A. E., Qureshi, M. M., Allsop, D., & El‐Agnaf, O. M. A. (2008) · Biochemistry · doi:10.1021/bi701415b · Cited by 166 · see citing works
Development of a Proteolytically Stable Retro-Inverso Peptide Inhibitor of β-Amyloid Oligomerization as a Potential Novel Treatment for Alzheimer’s Disease
Taylor, M., Moore, S., Mayes, J., Parkin, E. T., Beeg, M., Canovi, M., Gobbi, M., Mann, D. M. A., & Allsop, D. (2010) · Biochemistry · doi:10.1021/bi100144m · Cited by 162 · see citing works
Design and characterization of a membrane permeable N‐methyl amino acid‐containing peptide that inhibits Aβ1–40 fibrillogenesis
Gordon, D. J., Tappe, R., & Meredith, S. C. (2002) · Journal of Peptide Research · doi:10.1034/j.1399-3011.2002.11002.x · Cited by 158 · see citing works
The recombinant amyloid-beta peptide Abeta1-42 aggregates faster and is more neurotoxic than synthetic Abeta1-42.
Finder, V., Vodopivec, I., Nitsch, R., & Glockshuber, R. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2009.12.016 · Cited by 156 · see citing works
Branched KLVFF Tetramers Strongly Potentiate Inhibition of β‐Amyloid Aggregation
Chafekar, S. M., Malda, H., Merkx, M., Meijer, E. W., Viertl, D., Lashuel, H. A., Baas, F., & Scheper, W. (2007) · ChemBioChem · doi:10.1002/cbic.200700338 · Cited by 141 · see citing works
Beta Amyloid Aggregation Inhibitors: Small Molecules as Candidate Drugs for Therapy of Alzheimers Disease
Re, F., Airoldi, C., Zona, C., Masserini, M., Ferla, B. L., Quattrocchi, N., & Nicotra, F. (2010) · Current Medicinal Chemistry · doi:10.2174/092986710791959729 · Cited by 139 · see citing works
Kinetic characterization of amyloid-beta 1–42 aggregation with a multimethodological approach
Bartolini, M., Naldi, M., Fiori, J., Valle, F., Biscarini, F., Nicolau, D. V., & Andrisano, V. (2011) · Analytical Biochemistry · doi:10.1016/j.ab.2011.03.020 · Cited by 121 · see citing works
Probing the Role of Backbone Hydrogen Bonding in β-Amyloid Fibrils with Inhibitor Peptides Containing Ester Bonds at Alternate Positions
Gordon, D. J., & Meredith, S. C. (2002) · Biochemistry · doi:10.1021/bi0259857 · Cited by 110 · see citing works
Quantitative analysis of intrinsic and extrinsic factors in the aggregation mechanism of Alzheimer-associated Aβ-peptide
Meisl, G., Yang, X., Frohm, B., Knowles, T. P. J., & Linse, S. S. (2016) · Scientific Reports · doi:10.1038/srep18728 · Cited by 94 · see citing works
A Novel Retro-Inverso Peptide Inhibitor Reduces Amyloid Deposition, Oxidation and Inflammation and Stimulates Neurogenesis in the APPswe/PS1ΔE9 Mouse Model of Alzheimer’s Disease
Parthsarathy, V., McClean, P. L., Hölscher, C., Taylor, M., Tinker, C. L., Jones, G., Kolosov, O., Salvati, E., Gregori, M., Masserini, M., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054769 · Cited by 93 · see citing works
Advances in ion mobility spectrometry–mass spectrometry reveal key insights into amyloid assembly
Woods, L. A., Radford, S. E., & Ashcroft, A. E. (2012) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2012.10.002 · Cited by 93 · see citing works
Protection of primary neurons and mouse brain from Alzheimer's pathology by molecular tweezers
Attar, A., Ripoli, C., Riccardi, E., Maiti, P., Puma, D. D. L., Liu, T., Hayes, J. D., Jones, M. R., Lichti-Kaiser, K., Yang, F., et al. (2012) · Brain · doi:10.1093/brain/aws289 · Cited by 93 · see citing works
Rational Design of β-Sheet Ligands Against Aβ42-Induced Toxicity
Hochdörffer, K., März‐Berberich, J., Nagel‐Steger, L., Epple, M., Meyer‐Zaika, W., Horn, A. H. C., Sticht, H., Sinha, S., Bitan, G., & Schrader, T. H. (2011) · Journal of the American Chemical Society · doi:10.1021/ja107675n · Cited by 67 · see citing works
ESI-IMS–MS: A method for rapid analysis of protein aggregation and its inhibition by small molecules
Young, L. M., Saunders, J. C., Mahood, R. A., Revill, C., Foster, R. J., Ashcroft, A. E., & Radford, S. E. (2015) · Methods · doi:10.1016/j.ymeth.2015.05.017 · Cited by 66 · see citing works
Synthesis and Biological Evaluation of Clicked Curcumin and Clicked KLVFFA Conjugates as Inhibitors of β-Amyloid Fibril Formation
Ouberai, M. M., Dumy, P., Chierici, S., & Garcia, J. (2009) · Bioconjugate Chemistry · doi:10.1021/bc900281b · Cited by 61 · see citing works
Prevention of Alzheimer's Disease-associated Aβ Aggregation by Rationally Designed Nonpeptidic β-Sheet Ligands
Rzepecki, P., Nagel‐Steger, L., Feuerstein, S., Linne, U., Molt, O., Zadmard, R., Aschermann, K., Wehner, M., Schrader, T. H., & Riesner, D. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m405914200 · Cited by 54 · see citing works
C-Terminal Tetrapeptides Inhibit Aβ42-Induced Neurotoxicity Primarily through Specific Interaction at the N-Terminus of Aβ42
Li, H., Du, Z., Lopes, D. H. J., Fradinger, E. A., Wang, C., & Bitan, G. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm200982p · Cited by 43 · see citing works
Effects of Peptides Derived from Terminal Modifications of the Aβ Central Hydrophobic Core on Aβ Fibrillization
Bett, C. K., Serem, W. K., Fontenot, K. R., Hammer, R. P., & Garno, J. C. (2010) · ACS Chemical Neuroscience · doi:10.1021/cn900019r · Cited by 38 · see citing works
Medicinal value of asiaticoside for Alzheimer’s disease as assessed using single-molecule-detection fluorescence correlation spectroscopy, laser-scanning microscopy, transmission electron microscopy, and in silico docking
(2015) · doi:10.1186/s12906-015-0620-9 · Cited by 38 · see citing works
Structure−Activity Relationships in Peptide Modulators of β-Amyloid Protein Aggregation: Variation in α,α-Disubstitution Results in Altered Aggregate Size and Morphology
Bett, C. K., Ngunjiri, J. N., Serem, W. K., Fontenot, K. R., Hammer, R. P., McCarley, R. L., & Garno, J. C. (2010) · ACS Chemical Neuroscience · doi:10.1021/cn100045q · Cited by 34 · see citing works
Laser-Induced Liquid Bead Ion Desorption Mass Spectrometry: An Approach to Precisely Monitor the Oligomerization of the β-Amyloid Peptide
Cernescu, M., Stark, T., Kalden, E., Kurz, C., Leuner, K., Deller, T., Göbel, M., Eckert, G. P., & Brutschy, B. (2012) · Analytical Chemistry · doi:10.1021/ac300258m · Cited by 30 · see citing works
Simultaneous assessment of conformation and aggregation of β‐amyloid peptide using electrospray ionization mass spectrometry
Chen, X. G., Brining, S. K., Nguyen, V. Q., & Yergey, A. L. (1997) · The FASEB Journal · doi:10.1096/fasebj.11.10.9271367 · Cited by 21 · see citing works
MH84: A Novel γ-Secretase Modulator/PPARγ Agonist—Improves Mitochondrial Dysfunction in a Cellular Model of Alzheimer’s Disease
Pohland, M., Hagl, S., Pellowska, M., Wurglics, M., Schubert‐Zsilavecz, M., & Eckert, G. P. (2015) · Neurochemical Research · doi:10.1007/s11064-015-1765-0 · Cited by 14 · see citing works
A Palladium-Catalyzed Domino Reaction as Key Step for the Synthesis of Functionalized Aromatic Amino Acids
Göbel, M., Lautens, M., Stark, T., & Suhartono, M. (2013) · Synlett · doi:10.1055/s-0033-1339892 · Cited by 12 · see citing works

Flagged first, then by citations

Sorted by citations

Current and Future Treatments in Alzheimer Disease: An Update
Yiannopoulou, K. G., & Papageorgiou, S. G. (2020) · Journal of Central Nervous System Disease · doi:10.1177/1179573520907397 · Cited by 966 · see citing works
Therapeutic Approach to Alzheimer’s Disease: Current Treatments and New Perspectives
Pardo-Moreno, T., González-Acedo, A., Rivas-Domínguez, A., García-Morales, V., García-Cozar, F. J., Ramos-Rodríguez, J. J., & Melguizo-Rodríguez, L. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14061117 · Cited by 239 · see citing works
An update on the novel and approved drugs for Alzheimer disease
Alhazmi, H. A., & Albratty, M. (2022) · Saudi Pharmaceutical Journal · doi:10.1016/j.jsps.2022.10.004 · Cited by 122 · see citing works
“(Stark et al., 2017).”
Recent Applications of Retro-Inverso Peptides
Doti, N., Mardirossian, M., Sandomenico, A., Ruvo, M., & Caporale, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168677 · Cited by 93 · see citing works
A Hairpin Motif in the Amyloid-β Peptide Is Important for Formation of Disease-Related Oligomers
Khaled, M., Rönnbäck, I., Ilag, L. L., Gräslund, A., Strodel, B., & Österlund, N. (2023) · Journal of the American Chemical Society · doi:10.1021/jacs.3c03980 · Cited by 85 · see citing works
Peptide and protein mimetics by retro and retroinverso analogs
Rai, J. (2018) · Chemical Biology & Drug Design · doi:10.1111/cbdd.13472 · Cited by 51 · see citing works
Structural rearrangement of amyloid-β upon inhibitor binding suppresses formation of Alzheimer’s disease related oligomers
Lieblein, T., Zangl, R., Martin, J., Hoffmann, J., Hutchison, M.-T., Stark, T., Stirnal, E., Schrader, T. H., Schwalbe, H., & Morgner, N. (2020) · eLife · doi:10.7554/elife.59306 · Cited by 30 · see citing works
Advanced analytical methodologies in Alzheimer’s disease drug discovery
Simone, A. D., Naldi, M., Tedesco, D., Bartolini, M., Davani, L., & Andrisano, V. (2019) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2019.112899 · Cited by 22 · see citing works
New Insights into Alzheimer’s Disease: Novel Pathogenesis, Drug Target and Delivery
Chen, H., Xu, J., Xu, H., Luo, T., Li, Y., Jiang, K., Shentu, Y., & Tong, Z. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15041133 · Cited by 15 · see citing works
The Strategies of Development of New Non-Toxic Inhibitors of Amyloid Formation
Galzitskaya, O. V., Grishin, S. Y., Glyakina, A. V., Dovidchenko, N. V., Konstantinova, A. V., Kravchenko, S. V., & Surin, A. K. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043781 · Cited by 12 · see citing works
LILBID laser dissociation curves: a mass spectrometry-based method for the quantitative assessment of dsDNA binding affinities
Young, P., Hense, G., Immer, C., Wöhnert, J., & Morgner, N. (2020) · Scientific Reports · doi:10.1038/s41598-020-76867-9 · Cited by 12 · see citing works
Unveiling the inhibitory mechanism of peptidomimetic inhibitor against Aβ42 aggregation and protofibril disaggregation by molecular dynamics
Kaur, R., Saini, R. K., Singh, P., & Goyal, B. (2021) · Journal of Molecular Liquids · doi:10.1016/j.molliq.2021.116474 · Cited by 9 · see citing works
An Oligomannuronic Acid-Sialic Acid Conjugate Capable of Inhibiting Aβ42 Aggregation and Alleviating the Inflammatory Response of BV-2 Microglia
Wu, J., Wu, M., Zhang, H., Zhan, X., & Wu, N. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222212338 · Cited by 8 · see citing works
Tolcapone Derivative (Tol-D) Inhibits Aβ42 Fibrillogenesis and Ameliorates Aβ42-Induced Cytotoxicity and Cognitive Impairment
Chen, B., Mou, C., Guo, F.-Y., Sun, Q., Qu, L., Li, L., Cui, W., Lu, F., Jin, C. H., & Liu, F. (2022) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.1c00771 · Cited by 7 · see citing works
Podoplanin-positive cell-derived small extracellular vesicles contribute to cardiac amyloidosis after myocardial infarction
Cimini, M., Hansmann, U. H. E., González, C., Chesney, A. D., Truongcao, M. M., Gao, E., Wang, T., Roy, R., Forte, E., Mallaredy, V., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115408 · Cited by 5 · see citing works
Wie kleine Amyloid-β-Peptide zum großen Problem im Gehirn werden können
Zangl, R., & Morgner, N. (2021) · BIOspektrum · doi:10.1007/s12268-021-1678-1 · Cited by 1 · see citing works
Podoplanin Positive Cell-derived Extracellular Vesicles Contribute to Cardiac Amyloidosis After Myocardial InfarctionPreprint
Cimini, M., Hansmann, U. H. E., González, C., Chesney, A. D., Truongcao, M. M., Gao, E., Wang, T., Roy, R., Forte, E., Mallaredy, V., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.06.28.601297

Rationally Designed Peptidomimetic Modulators of Aβ Toxicity in Alzheimer's Disease
Rajasekhar, K., Suresh, S., Manjithaya, R. R., & Govindaraju, T. (2015) · Scientific Reports · doi:10.1038/srep08139 · Cited by 95 · see citing works
Design and Synthesis of a C 2-Symmetric Cyclic Decapeptide and Its Peptidomimetic as Potential Inhibitors against Amyloid-β Aggregation
Kobayakawa, T., Yamamoto, K., Tamamura, H., Fukutome, A., Arioka, M., & Tsuji, K. (2025) · Synlett · doi:10.1055/a-2536-8969
Rationally Designed Pentapeptide Analogs of Aβ19–23 Fragment as Potent Inhibitors of Aβ42 Aggregation
Baravkar, S. B., Lu, Y., Zhao, Q., Peng, H., Zhou, W. L., & Hong, S. (2025) · Molecules · doi:10.3390/molecules30092071 · Cited by 1 · see citing works
Convergent synthesis of peptidomimetic based on a chloroalkene dipeptide isostere and its application to inhibition against amyloid β aggregation
Kobayakawa, T., Azuma, C., Yamamoto, K., Tsuji, K., & Tamamura, H. (2024) · European Peptide Symposium (EPS) · doi:10.17952/37eps.2024.p1002
Synthesis and evaluation of ferrocenoyl pentapeptide (Fc-KLVFF) as an inhibitor of Alzheimer’s Aβ1–42 fibril formation in vitro
Wei, C., Peng, Y., Zhang, L., Huang, Q., Cheng, M. H., Liu, Y., & Li, J. (2011) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2011.07.111 · Cited by 50 · see citing works

Authors: Stark, T., Lieblein, T., Pohland, M., Kalden, E., Freund, P., Zangl, R., Grewal, R., Heilemann, M., Eckert, G. P., Morgner, N., & Göbel, M. W.
Affiliations: Goethe University Frankfurt (DE)
Justus-Liebig-Universität Gießen (DE)
Corresponding author: Göbel, Michael W.
ORCID: Lieblein, Tobias
Zangl, René
Heilemann, Mike
Eckert, Gunter P.
Morgner, Nina
Göbel, Michael W.
Venue: Biochemistry
Publisher: American Chemical Society (ACS)
Published: 2017-08-25
Volume: 56
Issue: 36
Pages: 4840-4849
ISSN: 0006-2960 (ISSN-L)
1520-4995
DOI: 10.1021/acs.biochem.7b00223
OpenAlex: W2750503782
Cited by: 17
References: 54
Citations by year: 2025: 1 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 1 · 2018: 1
FWCI: 1.01
Type: journal article
Language: en
Open access: closed
Locations: Biochemistry (publishedVersion)
PubMed (publishedVersion)
Funders: Deutsche Forschungsgemeinschaft (1986)
European Commission (337567)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
Keywords: peptidomimetics, amyloid-beta 42, peptide aggregation inhibition, Alzheimer's disease, KLVFF peptide, Catellani reaction, palladium-catalyzed cross-coupling, aromatic amino acid substitution, amyloid fibrils, thioflavin T binding, peptide stability
MeSH terms: Cell Line, Cell Survival, Humans, Peptide Fragments, Protein Binding, Molecular Structure, Amyloid beta-Peptides, Lactate Dehydrogenases, Cell Proliferation, Peptidomimetics

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Peptidomimetics That Inhibit and Partially Reverse the Aggregation of Aβ1–42

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks