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Molecular tweezers, and molecular clips, are host molecules with open cavities capable of binding guest molecules.^[3] The open cavity of the molecular tweezers may bind guests using non-covalent bonding, which includes hydrogen bonding, metal coordination, hydrophobic forces, van der Waals forces, π–π interactions, and/or electrostatic effects. These complexes are a subset of macrocyclic molecular receptors and their structure is that the two "arms" that bind the guest molecule between them are only connected at one end leading to a certain flexibility of these receptor molecules (induced fit model).

History

The term "molecular tweezers" was first used by Whitlock.^[4] The class of hosts was developed and popularized by Zimmerman in the mid-1980s to early 1990s^[5]^[6]^[7] and later by Klärner.^[8]

Examples

Some molecular tweezers bind aromatic guests.^[1] These molecular tweezers consist of a pair of anthracene arms held at a distance that allows aromatic guests to gain π–π interactions from both (see Figure). Other molecular tweezers feature a pair of tethered porphyrins.^[9]

Yet another type of molecular tweezers bind fullerenes.^[2] Such "buckycatchers" are composed of two corannulene pincers that complement the surface of the convex fullerene guest (Figure 2). An association constant (K_a) of 8,600 M⁻¹ was calculated using ¹H NMR spectroscopy.

Stoermer and co-workers described clefts capable of capturing cyclohexane or chloroform molecules. Intriguingly, pi interactions played key roles in guest capture as well as cleft formation rate.^[10]

Figure 3. The aliphatic sidechain of lysine bound inside the cavity of the phosphate-substituted molecular benzene tweezer by electrostatic, CH-p and hydrophobic interactions reported by Klärner, Schrader, and coworkers.^[9,10]

Water-soluble phosphate-substituted molecular tweezers made of alternating phenyl and norbornenyl substituents bind to positively charged aliphatic side chains of basic amino acids, such as lysine and arginine (Figure 3).^[11]^[12] Similar compounds called "molecular clips", whose side walls are flat rather than convex, prefer to enclose flat pyridinium rings (for example the nicotinamide ring of NAD(P)+) between their plane naphthalene sidewalls (Figure 4).^[13] These mutually exclusive binding modes make these compounds valuable tools for probing critical biological interactions of basic amino acid side chains in peptides and proteins as well as of NAD(P)⁺ and similar cofactors. For example, both types of compounds inhibit the oxidation reactions of ethanol by alcohol dehydrogenase or of glucose-6-phosphate by glucose-6-phosphate dehydrogenase,^[14] respectively.

Figure 4. The double-sandwich host–guest complex of the phosphate-substituted molecular clip and nicotinamide adenine dinucleotide (NAD⁺, the cofactor of many redox enzymes). The nicotinamide ring (the active site of NAD⁺) is bound between the clip naphthalene sidewalls, as reported by Klärner, Schrader, Ochsenfeld, and coworkers.^[11]

The molecular tweezers, but not the clips, efficiently inhibit the formation of toxic oligomers and aggregates by amyloidogenic proteins associated with different diseases. Examples include the proteins involved in Alzheimer's disease – amyloid β-protein (Aβ) and tau;^[15]^[16]^[17] α-synuclein, which is thought to cause Parkinson's disease and other synucleinopathies^[18]^[19]^[20]^[21] and is involved in spinal-cord injury;^[22] mutant huntingtin, which causes Huntington's disease;^[23] islet amyloid polypeptide (amylin), which kills pancreatic β-cells in type-2 diabetes;^[24] transthyretin (TTR), which causes familial amyloid polyneuropathy, familial amyloid cardiomyopathy, and senile systemic amyloidosis;^[25] aggregation-prone mutants of the tumor-suppressor protein p53;^[26] and semen proteins whose aggregation enhances HIV infection.^[27] Importantly, the molecular tweezers have been found to be effective and safe not only in the test tube but also in animal models of different diseases,^[28]^[29] suggesting that they may be developed as drugs against diseases caused by abnormal protein aggregation, all of which currently have no cure. They were also shown to destroy the membranes of enveloped viruses, such as HIV, herpes, and hepatitis C,^[27] which makes them good candidates for development of microbicides.

The above examples show the potential reactivity and specificity of these molecules. The binding cavity between the side arms of the tweezer can evolve to bind to an appropriate guest with high specificity, depending on the configuration of the tweezer. That makes this overall class of macromolecule truly synthetic molecular receptors with important application to biology and medicine.^[30]^[31]^[32]

References

^ ^a ^b A. Petitjean; R. G. Khoury; N. Kyritsakas; J. M. Lehn (2004). "Dynamic Devices. Shape Switching and Substrate Binding in Ion-Controlled Nanomechanical Molecular Tweezers". J. Am. Chem. Soc. 126 (21): 6637–6647. Bibcode:2004JAChS.126.6637P. doi:10.1021/ja031915r. PMID 15161291.
^ ^a ^b A. Sygula; F. R. Fronczek; R. Sygula; P. W. Rabideau; M. M. Olmstead (2007). "A Double Concave Hydrocarbon Buckycatcher". J. Am. Chem. Soc. 129 (13): 3842–3843. Bibcode:2007JAChS.129.3842S. doi:10.1021/ja070616p. PMID 17348661. S2CID 25154754.
^ Hardouin-Lerouge, M.; Hudhomme, P.; Salle, M. (2011). "Molecular clips and tweezers hosting neutral guests" (PDF). Chemical Society Reviews. 40 (1): 30–43. doi:10.1039/B915145C. PMID 21038068.
^ Chen C.-W.; Whitlock H. W. "Molecular Tweezers – A Simple-Model of Bifunctional Intercalation", J. Am. Chem. Soc. 1978, 100, 4921
^ Zimmerman, S. C.; VanZyl, C. M. "Rigid molecular tweezers: synthesis, characterization, and complexation chemistry of a diacridine", J. Am. Chem. Soc. 1987, 109, 7894.
^ Zimmerman, S. C.; Wu, W. "A rigid molecular tweezers with an active site carboxylic acid: exceptionally efficient receptor for adenine in an organic solvent", J. Am. Chem. Soc. 1989, 111, 8054.
^ Zimmerman, S. C. "Rigid molecular tweezers as hosts for the complexation of neutral guests", Top. Curr. Chem. 1993, 165, 71.
^ F.-G. Klärner & B. Kahlert (2003). "Molecular Tweezers and Clips as Synthetic Receptors. Molecular Recognition and Dynamics in Receptor-Substrate Complexes". Acc. Chem. Res. 36 (12): 919–932. doi:10.1021/ar0200448. PMID 14674783. S2CID 29313731.
^ X. Huang; N. Fujioka; G. Pescitelli; F. Koehn; R. T. Williamson; K. Nakanishi; N. Berova (2002). "Absolute Configurational Assignments of Secondary Amines by CD-sensitive Dimeric Zinc Porphyrin Host". J. Am. Chem. Soc. 124 (17): 10320–10335. Bibcode:2002JAChS.12410320H. doi:10.1021/ja020520p. PMID 12197735. S2CID 33852448.
^ Stoermer, Martin J.; Wickramasinghe, Wasantha A.; Byriel, Karl A.; Hockless, David C. R.; Skelton, Brian W.; Sobolev, Alexandre N.; White, Allan H.; Mak, Jeffrey Y. W.; Fairlie, David P. (2017-12-08). "Stereoelectronic Effects on Dienophile Separation Influence the Diels–Alder Synthesis of Molecular Clefts" (PDF). European Journal of Organic Chemistry. 2017 (45): 6793–6796. doi:10.1002/ejoc.201701319. ISSN 1099-0690.
^ M Fokkens, T Schrader, and F-G Klärner. A molecular tweezer for lysine and arginine. J. Am. Chem. Soc. 2005; 127: 14415–14421.
^ P. Talbiersky; F. Bastkowski; F.-G. Klärner; T. Schrader (2008). "Molecular Clip and Tweezer Introduce New Mechanisms of Enzyme Inhibition". J. Am. Chem. Soc. 130 (30): 9824–9828. Bibcode:2008JAChS.130.9824T. doi:10.1021/ja801441j. PMID 18605724.
^ J. Polkowska; F. Bastkowski; T. Schrader; F.-G. Klärner; J. Zienau; F. Koziol; C. Ochsenfeld (2009). "A combined experimental and theoretical study of the pH-dependent binding mode of NAD+ by water-soluble molecular clips". J. Phys. Org. Chem. 22 (30): 779–790. doi:10.1002/poc.1519.
^ M. Kirsch; P. Talbiersky; J. Polkowska; F. Bastkowski; T. Schaller; H. de Groot; F.-G. Klärner; T. Schrader (2009). "A Mechanism of Efficient G6PD Inhibition by a Molecular Clip". Angew. Chem. Int. Ed. 48 (16): 2886–2890. doi:10.1002/anie.200806175. PMID 19283805.
^ S Sinha, DHJ Lopes, Z Du, ES Pang, A Shanmugam, A Lomakin, P Talbiersky, A Tennstaedt, K McDaniel, R Bakshi, P-Y Kuo, M Ehrmann, GB Benedek, JA Loo, F-G Klärner, T Schrader, C Wang, and G Bitan. Lysine-specific molecular tweezers are broad-spectrum inhibitor of aggregation and toxicity of amyloid proteins. J. Am. Chem. Soc. 2011; 133(42): 16958–16969.
^ S Sinha, Z Du, P Maiti, F-G Klärner, T Schrader, C Wang, and G Bitan. Comparison of Three Amyloid Assembly Inhibitors: The Sugar scyllo-Inositol, the Polyphenol Epigallocatechin Gallate, and the Molecular Tweezer CLR01. ACS Chem. Neurosci. 2012; 3(6): 451–458.
^ X Zheng, D-Y Liu, F-G Klärner, T Schrader, G Bitan, and MT Bowers. Amyloid β-protein Assembly: The Effect of Molecular Tweezer CLR01 and CLR03. J. Phys. Chem. B, 2015; 119: 4831–4841.
^ S Prabhudesai*, S Sinha*, A Attar, A Kotagiri, AG Fitzmaurice, R Lakshmanan, MI Ivanova, JA Loo, F-G Klärner, T Schrader, M Stahl, G Bitan#, and JM Bronstein#. A Novel "Molecular Tweezer" Inhibitor of α-Synuclein Neurotoxicity in Vitro and in Vivo. Neurotherapeutics. 2012; 9(2): 464–476.
^ S Acharya, BM Safaie, P Wongkongkathep, MI Ivanova, A Attar, F-G Klärner, T Schrader, JA Loo, G Bitan, and LJ Lapidus. Molecular Basis for Preventing α-Synuclein Aggregation by a Molecular Tweezer. J. Biol. Chem. 2014; 289(15): 10727–10737.
^ A Lulla, L Barnhill, G Bitan, MI Ivanova, B Nguyen, K O'Donnell, MC Stahl, C Yamashiro, F-G Klärner, T Schrader, A Sagasti, and JM Bronstein, Environ. Health Perspect. 2016; 124: 1766–1775. Archived 2017-07-05 at the Wayback Machine
^ Richter, Franziska; Subramaniam, Sudhakar R.; Magen, Iddo; Lee, Patrick; Hayes, Jane; Attar, Aida; Zhu, Chunni; Franich, Nicholas R.; Bove, Nicholas (2017-06-05). "A Molecular Tweezer Ameliorates Motor Deficits in Mice Overexpressing α-Synuclein". Neurotherapeutics. 14 (4): 1107–1119. doi:10.1007/s13311-017-0544-9. ISSN 1933-7213. PMC 5722755. PMID 28585223.
^ SM Fogerson, AJ van Brummen, DJ Busch, SR Allen, R Roychaudhuri, S Banks, F-G Klärner, T Schrader, G Bitan, and JR Morgan, Reducing synuclein accumulation improves neuronal survival after spinal cord injury, Exp. Neurol. 2016; 278: 105–115.
^ Vöpel, Tobias; Bravo-Rodriguez, Kenny; Mittal, Sumit; Vachharajani, Shivang; Gnutt, David; Sharma, Abhishek; Steinhof, Anne; Fatoba, Oluwaseun; Ellrichmann, Gisa (2017-04-26). "Inhibition of Huntingtin Exon-1 Aggregation by the Molecular Tweezer CLR01". Journal of the American Chemical Society. 139 (16): 5640–5643. Bibcode:2017JAChS.139.5640V. doi:10.1021/jacs.6b11039. ISSN 0002-7863. PMC 5506490. PMID 28406616.
^ DHJ Lopes, A Attar, G Nair, EY Hayden, Z Du, K McDaniel, S Dutt, K Bravo-Rodriguez, S Mittal, F-G Klärner, C Wang, E Sanchez-Garcia, T Schrader, and G Bitan (2015) Molecular tweezers inhibit islet amyloid polypeptide assembly and toxicity by a new mechanism, ACS Chem. Biol. 2015; 10: 1555–1569.
^ N Ferreira, A Pereira-Henriques, A Attar, F-G Klärner, T Schrader, G Bitan, L Gales, MJ Saraiva, and MR Almeida. Molecular Tweezers Targeting Transthyretin Amyloidosis. Neurotherapeutics. 2014; 11: 450–461.
^ G Herzog, MD Shmueli, L Levi, L Engel, E Gazit, F-G Klärner, T Schrader, G Bitan, and D Segal. The Lys-specific molecular tweezer, CLR01, modulates aggregation of mutant p53 DNA binding domain and inhibits its toxicity, Biochemistry, 2015; 54: 3729–3738.
^ ^a ^b E Lump, LM Castellano, C Meier, J Seeliger, N Erwin, B Sperlich, CM Stürzel, S Usmani, RM Hammond, J von Einem, G Gerold, F Kreppel, K Bravo-Rodriguez, T Pietschmann, VM Holmes, D Palesch, O Zirafi, D Weissman, A Sowislok, B Wettig, C Heid, F Kirchhoff, T Weil, F-G Klärner, T Schrader, G Bitan, E Sanchez-Garcia, R Winter, J Shorter, and Jan Münch, A molecular tweezer antagonizes seminal amyloids and HIV infection, eLife, 2015; 4:e05397.
^ A Attar, C Ripoli, E Riccardi, P Maiti, DD Li Puma, T Liu, J Hayes, MR Jones, K Lichti-Kaiser, F Yang, GD Gale, C-h Tseng, M Tan, C-W Xie, JL Straudinger, F-G Klärner, T Schrader, SA Frautschy, C Grassi and G Bitan. Protection of primary neurons and mouse brain from Alzheimer's pathology by molecular tweezers. Brain. 2012; 135(Pt 12): 3735–3748.
^ A Attar, W-TC Chan, F-G Klärner, T Schrader, and G Bitan. Safety and pharmacological characterization of the molecular tweezer CLR01 – a broad-spectrum inhibitor of amyloid proteins' toxicity. BMC Pharm. Tox. 2014; 15(23): doi:10.1186/2050-6511-15-23.
^ F-G Klärner and T Schrader. Aromatic Interactions by Molecular Tweezers and Clips in Chemical and Biological Systems. Acc. Chem. Res. 2013; 46: 967–978.
^ A Attar and G Bitan. Disrupting self-assembly and toxicity of amyloidogenic protein oligomers by "molecular tweezers" – from the test tube to animal models, Curr. Pharm. Des. 2014; 20: 2469–2483.
^ T Schrader, G Bitan, and F-G Klärner, Molecular Tweezers for Lysine and Arginine – Powerful Inhibitors of Pathologic Protein Aggregation, Chem. Commun. 2016: 52: 11318–11334.

External links

Journal of Chemical Education Featured Molecules December 2004: Nanoscale Molecular Tweezers and article^{[permanent dead link‍]}
Crystalmaker molecular tweezers

[lehn-1] A. Petitjean; R. G. Khoury; N. Kyritsakas; J. M. Lehn (2004). "Dynamic Devices. Shape Switching and Substrate Binding in Ion-Controlled Nanomechanical Molecular Tweezers". J. Am. Chem. Soc. 126 (21): 6637–6647. Bibcode:2004JAChS.126.6637P. doi:10.1021/ja031915r. PMID 15161291.

[sygula-2] A. Sygula; F. R. Fronczek; R. Sygula; P. W. Rabideau; M. M. Olmstead (2007). "A Double Concave Hydrocarbon Buckycatcher". J. Am. Chem. Soc. 129 (13): 3842–3843. Bibcode:2007JAChS.129.3842S. doi:10.1021/ja070616p. PMID 17348661. S2CID 25154754.

[3] Hardouin-Lerouge, M.; Hudhomme, P.; Salle, M. (2011). "Molecular clips and tweezers hosting neutral guests" (PDF). Chemical Society Reviews. 40 (1): 30–43. doi:10.1039/B915145C. PMID 21038068.

[4] Chen C.-W.; Whitlock H. W. "Molecular Tweezers – A Simple-Model of Bifunctional Intercalation", J. Am. Chem. Soc. 1978, 100, 4921

[5] Zimmerman, S. C.; VanZyl, C. M. "Rigid molecular tweezers: synthesis, characterization, and complexation chemistry of a diacridine", J. Am. Chem. Soc. 1987, 109, 7894.

[6] Zimmerman, S. C.; Wu, W. "A rigid molecular tweezers with an active site carboxylic acid: exceptionally efficient receptor for adenine in an organic solvent", J. Am. Chem. Soc. 1989, 111, 8054.

[7] Zimmerman, S. C. "Rigid molecular tweezers as hosts for the complexation of neutral guests", Top. Curr. Chem. 1993, 165, 71.

[8] F.-G. Klärner & B. Kahlert (2003). "Molecular Tweezers and Clips as Synthetic Receptors. Molecular Recognition and Dynamics in Receptor-Substrate Complexes". Acc. Chem. Res. 36 (12): 919–932. doi:10.1021/ar0200448. PMID 14674783. S2CID 29313731.

[berova-9] X. Huang; N. Fujioka; G. Pescitelli; F. Koehn; R. T. Williamson; K. Nakanishi; N. Berova (2002). "Absolute Configurational Assignments of Secondary Amines by CD-sensitive Dimeric Zinc Porphyrin Host". J. Am. Chem. Soc. 124 (17): 10320–10335. Bibcode:2002JAChS.12410320H. doi:10.1021/ja020520p. PMID 12197735. S2CID 33852448.

[10] Stoermer, Martin J.; Wickramasinghe, Wasantha A.; Byriel, Karl A.; Hockless, David C. R.; Skelton, Brian W.; Sobolev, Alexandre N.; White, Allan H.; Mak, Jeffrey Y. W.; Fairlie, David P. (2017-12-08). "Stereoelectronic Effects on Dienophile Separation Influence the Diels–Alder Synthesis of Molecular Clefts" (PDF). European Journal of Organic Chemistry. 2017 (45): 6793–6796. doi:10.1002/ejoc.201701319. ISSN 1099-0690.

[11] M Fokkens, T Schrader, and F-G Klärner. A molecular tweezer for lysine and arginine. J. Am. Chem. Soc. 2005; 127: 14415–14421.

[talbiersky-12] P. Talbiersky; F. Bastkowski; F.-G. Klärner; T. Schrader (2008). "Molecular Clip and Tweezer Introduce New Mechanisms of Enzyme Inhibition". J. Am. Chem. Soc. 130 (30): 9824–9828. Bibcode:2008JAChS.130.9824T. doi:10.1021/ja801441j. PMID 18605724.

[polkowska-13] J. Polkowska; F. Bastkowski; T. Schrader; F.-G. Klärner; J. Zienau; F. Koziol; C. Ochsenfeld (2009). "A combined experimental and theoretical study of the pH-dependent binding mode of NAD+ by water-soluble molecular clips". J. Phys. Org. Chem. 22 (30): 779–790. doi:10.1002/poc.1519.

[kirsch-14] M. Kirsch; P. Talbiersky; J. Polkowska; F. Bastkowski; T. Schaller; H. de Groot; F.-G. Klärner; T. Schrader (2009). "A Mechanism of Efficient G6PD Inhibition by a Molecular Clip". Angew. Chem. Int. Ed. 48 (16): 2886–2890. doi:10.1002/anie.200806175. PMID 19283805.

[15] S Sinha, DHJ Lopes, Z Du, ES Pang, A Shanmugam, A Lomakin, P Talbiersky, A Tennstaedt, K McDaniel, R Bakshi, P-Y Kuo, M Ehrmann, GB Benedek, JA Loo, F-G Klärner, T Schrader, C Wang, and G Bitan. Lysine-specific molecular tweezers are broad-spectrum inhibitor of aggregation and toxicity of amyloid proteins. J. Am. Chem. Soc. 2011; 133(42): 16958–16969.

[16] S Sinha, Z Du, P Maiti, F-G Klärner, T Schrader, C Wang, and G Bitan. Comparison of Three Amyloid Assembly Inhibitors: The Sugar scyllo-Inositol, the Polyphenol Epigallocatechin Gallate, and the Molecular Tweezer CLR01. ACS Chem. Neurosci. 2012; 3(6): 451–458.

[17] X Zheng, D-Y Liu, F-G Klärner, T Schrader, G Bitan, and MT Bowers. Amyloid β-protein Assembly: The Effect of Molecular Tweezer CLR01 and CLR03. J. Phys. Chem. B, 2015; 119: 4831–4841.

[18] S Prabhudesai*, S Sinha*, A Attar, A Kotagiri, AG Fitzmaurice, R Lakshmanan, MI Ivanova, JA Loo, F-G Klärner, T Schrader, M Stahl, G Bitan#, and JM Bronstein#. A Novel "Molecular Tweezer" Inhibitor of α-Synuclein Neurotoxicity in Vitro and in Vivo. Neurotherapeutics. 2012; 9(2): 464–476.

[19] S Acharya, BM Safaie, P Wongkongkathep, MI Ivanova, A Attar, F-G Klärner, T Schrader, JA Loo, G Bitan, and LJ Lapidus. Molecular Basis for Preventing α-Synuclein Aggregation by a Molecular Tweezer. J. Biol. Chem. 2014; 289(15): 10727–10737.

[20] A Lulla, L Barnhill, G Bitan, MI Ivanova, B Nguyen, K O'Donnell, MC Stahl, C Yamashiro, F-G Klärner, T Schrader, A Sagasti, and JM Bronstein, Environ. Health Perspect. 2016; 124: 1766–1775. Archived 2017-07-05 at the Wayback Machine

[21] Richter, Franziska; Subramaniam, Sudhakar R.; Magen, Iddo; Lee, Patrick; Hayes, Jane; Attar, Aida; Zhu, Chunni; Franich, Nicholas R.; Bove, Nicholas (2017-06-05). "A Molecular Tweezer Ameliorates Motor Deficits in Mice Overexpressing α-Synuclein". Neurotherapeutics. 14 (4): 1107–1119. doi:10.1007/s13311-017-0544-9. ISSN 1933-7213. PMC 5722755. PMID 28585223.

[22] SM Fogerson, AJ van Brummen, DJ Busch, SR Allen, R Roychaudhuri, S Banks, F-G Klärner, T Schrader, G Bitan, and JR Morgan, Reducing synuclein accumulation improves neuronal survival after spinal cord injury, Exp. Neurol. 2016; 278: 105–115.

[23] Vöpel, Tobias; Bravo-Rodriguez, Kenny; Mittal, Sumit; Vachharajani, Shivang; Gnutt, David; Sharma, Abhishek; Steinhof, Anne; Fatoba, Oluwaseun; Ellrichmann, Gisa (2017-04-26). "Inhibition of Huntingtin Exon-1 Aggregation by the Molecular Tweezer CLR01". Journal of the American Chemical Society. 139 (16): 5640–5643. Bibcode:2017JAChS.139.5640V. doi:10.1021/jacs.6b11039. ISSN 0002-7863. PMC 5506490. PMID 28406616.

[24] DHJ Lopes, A Attar, G Nair, EY Hayden, Z Du, K McDaniel, S Dutt, K Bravo-Rodriguez, S Mittal, F-G Klärner, C Wang, E Sanchez-Garcia, T Schrader, and G Bitan (2015) Molecular tweezers inhibit islet amyloid polypeptide assembly and toxicity by a new mechanism, ACS Chem. Biol. 2015; 10: 1555–1569.

[25] N Ferreira, A Pereira-Henriques, A Attar, F-G Klärner, T Schrader, G Bitan, L Gales, MJ Saraiva, and MR Almeida. Molecular Tweezers Targeting Transthyretin Amyloidosis. Neurotherapeutics. 2014; 11: 450–461.

[26] G Herzog, MD Shmueli, L Levi, L Engel, E Gazit, F-G Klärner, T Schrader, G Bitan, and D Segal. The Lys-specific molecular tweezer, CLR01, modulates aggregation of mutant p53 DNA binding domain and inhibits its toxicity, Biochemistry, 2015; 54: 3729–3738.

[eLife,_2015;_4:e05397-27] E Lump, LM Castellano, C Meier, J Seeliger, N Erwin, B Sperlich, CM Stürzel, S Usmani, RM Hammond, J von Einem, G Gerold, F Kreppel, K Bravo-Rodriguez, T Pietschmann, VM Holmes, D Palesch, O Zirafi, D Weissman, A Sowislok, B Wettig, C Heid, F Kirchhoff, T Weil, F-G Klärner, T Schrader, G Bitan, E Sanchez-Garcia, R Winter, J Shorter, and Jan Münch, A molecular tweezer antagonizes seminal amyloids and HIV infection, eLife, 2015; 4:e05397.

[28] A Attar, C Ripoli, E Riccardi, P Maiti, DD Li Puma, T Liu, J Hayes, MR Jones, K Lichti-Kaiser, F Yang, GD Gale, C-h Tseng, M Tan, C-W Xie, JL Straudinger, F-G Klärner, T Schrader, SA Frautschy, C Grassi and G Bitan. Protection of primary neurons and mouse brain from Alzheimer's pathology by molecular tweezers. Brain. 2012; 135(Pt 12): 3735–3748.

[29] A Attar, W-TC Chan, F-G Klärner, T Schrader, and G Bitan. Safety and pharmacological characterization of the molecular tweezer CLR01 – a broad-spectrum inhibitor of amyloid proteins' toxicity. BMC Pharm. Tox. 2014; 15(23): doi:10.1186/2050-6511-15-23.

[30] F-G Klärner and T Schrader. Aromatic Interactions by Molecular Tweezers and Clips in Chemical and Biological Systems. Acc. Chem. Res. 2013; 46: 967–978.

[31] A Attar and G Bitan. Disrupting self-assembly and toxicity of amyloidogenic protein oligomers by "molecular tweezers" – from the test tube to animal models, Curr. Pharm. Des. 2014; 20: 2469–2483.

[32] T Schrader, G Bitan, and F-G Klärner, Molecular Tweezers for Lysine and Arginine – Powerful Inhibitors of Pathologic Protein Aggregation, Chem. Commun. 2016: 52: 11318–11334.

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PROFILPELAJAR.COM

Molecular tweezers

History

Examples

See also

References

External links

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