344950-59-0Relevant academic research and scientific papers
Design and synthesis of fluorescent probe for polyhistidine tag using macrocyclic nickel(II) complex and fluorescein conjugate
Taki, Masayasu,Asahi, Fumiyoshi,Hirayama, Tasuku,Yamamoto, Yukio
, p. 386 - 394 (2011)
We report a newly designed polyhistidine tag (His-tag) targeting fluorescent probe, NiLODCF, which we synthesized based on the fluorophore displacement mechanism. A macrocyclic nickel(II) complex (NiL O) was employed as a novel binding site for a His-tag motif, and we chose dichlorofluorescein (DCF) (=2′,7′-dichloro-3′,6′- dihydroxyspiro[iso-benzofuran-1(3H),9′-(9H)xanthen]-3-one) as the fluorophore. A hypochromic shift of NiLODCF from the metal-unbound form (L ODCF) in the absorption spectrum suggested that the phenolic oxygen atom of DCF interacted directly with the NiLO complex, resulting in efficient fluorescence quenching (Φ = 0.084) in a neutral aqueous solution. When a model peptide having a hexahistidine sequence (H6Y1: YHHHHHH) was added to the solution of NiLODCF, a significant fluorescence enhancement in the emission (Φ = 0.60) was observed. The stoichiometry of the ternary complex between NiLODCF and H6Y1 was 1:1. The fluorescence intensity increased as the concentration of H6Y1 increased, and the dissociation constant (Kd) was determined to be 24 ± 1 μM, consistent with that for the Ni-NTA complex and His6-fused proteins (Kd = 1-20 μM). These results indicate that macrocyclic NiLO can serve as a novel binding site for the polyhistidine sequence and that NiLODCF would be applicable to a switchable fluorescent probe for such His-tagged proteins.
Synthesis and structure-activity relationships of azamacrocyclic C-X-C chemokine receptor 4 antagonists: Analogues containing a single azamacrocyclic ring are potent inhibitors of T-cell tropic (X4) HIV-1 replication
Bridger, Gary J.,Skerlj, Renato T.,Hernandez-Abad, Pedro E.,Bogucki, David E.,Wang, Zhongren,Zhou, Yuanxi,Nan, Susan,Boehringer, Eva M.,Wilson, Trevor,Crawford, Jason,Metz, Markus,Hatse, Sigrid,Princen, Katrien,De Clercq, Erik,Schols, Dominique
supporting information; experimental part, p. 1250 - 1260 (2010/08/07)
Bis-tetraazamacrocycles such as the bicyclam AMD3100 (1) are a class of potent and selective anti-HIV-1 agents that inhibit virus replication by binding to the chemokine receptor CXCR4, the coreceptor for entry of X4 viruses. By sequential replacement and/or deletion of the amino groups within the azamacrocyclic ring systems, we have determined the minimum structural features required for potent antiviral activity in this class of compounds. All eight amino groups are not required for activity, the critical amino groups on a per ring basis are nonidentical, and the overall charge at physiological pHcan be reduced without compromising potency. This approach led to the identification of several single ring azamacrocyclic analogues such as AMD3465 (3d), 36, and 40, which exhibit EC50's against the cytopathic effects of HIV-1 of 9.0, 1.0, and 4.0 nM, respectively, antiviral potencies that are comparable to 1 (EC50 against HIV-1 of 4.0 nM). More importantly, however, the key structural elements of 1 required for antiviral activitymay facilitate the design of nonmacrocyclic CXCR4 antagonists suitable for HIV treatment via oral administration. 2009 American Chemical Society.
