Molecular tweezers
Molecular tweezers, and molecular clips, are host
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
Yet another type of molecular tweezers bind
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]
Water-soluble phosphate-substituted molecular tweezers made of alternating
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
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]
See also
References
- ^ PMID 15161291.
- ^ S2CID 25154754.
- 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.
- S2CID 29313731.
- S2CID 33852448.
- 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.
- PMID 18605724.
- doi:10.1002/poc.1519.
- 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
- 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.
- 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