Title |
Fragment based search for small molecule inhibitors of HIV-1 Tat-TAR
|
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Published in |
Bioorganic & Medicinal Chemistry Letters, November 2014
|
DOI | 10.1016/j.bmcl.2014.11.004 |
Pubmed ID | |
Authors |
Mirco Zeiger, Sebastian Stark, Elisabeth Kalden, Bettina Ackermann, Jan Ferner, Ute Scheffer, Fatemeh Shoja-Bazargani, Veysel Erdel, Harald Schwalbe, Michael W. Göbel |
Abstract |
Basic molecular building blocks such as benzene rings, amidines, guanidines, and amino groups have been combined in a systematic way to generate ligand candidates for HIV-1 TAR RNA. Ranking of the resulting compounds was achieved in a fluorimetric Tat-TAR competition assay. Although simple molecules such as phenylguanidine are inactive, few iteration steps led to a set of ligands with IC50 values ranging from 40 to 150 μM. 1,7-Diaminoisoquinoline 17 and 2,4,6-triaminoquinazoline 22 have been further characterized by NMR titrations with TAR RNA. Compound 22 is bound to TAR at two high affinity sites and shows slow exchange between the free ligand and the RNA complex. These results encourage investigations of dimeric ligands built from two copies of compound 22 or related heterocycles. |
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Geographical breakdown
Country | Count | As % |
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Unknown | 50 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 15 | 30% |
Student > Master | 7 | 14% |
Student > Bachelor | 5 | 10% |
Researcher | 5 | 10% |
Professor > Associate Professor | 2 | 4% |
Other | 5 | 10% |
Unknown | 11 | 22% |
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Medicine and Dentistry | 2 | 4% |
Other | 3 | 6% |
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