分子ピンセットまたは分子クリップは、ゲスト分子を挟み込むことができる開放性の空洞をもつ非環状のホスト分子である。「分子ピンセット」という用語は、Howard J. Whitlockが最初に使用した[1]。しかし、この種のホスト分子は、1980年代中頃から1990年代初頭にかけてSteven C. Zimmermanによって研究開発され広まった[2][3][4]、近年では、Frank-Gerrit Klärnerらにより研究されている[5]。分子ピンセットの開放性空洞はホスト分子を非共有性結合で結び付ける。非共有性結合には水素結合、金属配位、 疎水性相互作用、ファンデルワールス力、π-π相互作用、静電効果のいずれかまたは任意の組み合わせが含まれる。このホスト-ゲスト複合体は大環状分子受容体の一部分とみなすことができ、またゲスト分子を挟み込む2つの「アーム」をもった構造であり、そのアームの片方の端だけが固定されているので、ある程度の柔軟性を示す(誘導適合モデル)。
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Zimmerman, S. C.; Wu, W.(1989¥volume= 111).“A rigid molecular tweezers with an active site carboxylic acid: exceptionally efficient receptor for adenine in an organic solvent”.J. Am. Chem. Soc.: 8054-8055.doi:10.1021/ja00202a077.
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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.
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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.
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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.
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.
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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.
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.
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