7PNL
Complex between monomolecular human telomeric G-quadruplex and a sulfonamide derivative of the natural alkaloid Berberine
Summary for 7PNL
| Entry DOI | 10.2210/pdb7pnl/pdb |
| Descriptor | G-guadruplex DNA (23-mer), POTASSIUM ION, 4-[[1-[3-[(17-methoxy-5,7-dioxa-13-azoniapentacyclo[11.8.0.0^{2,10}.0^{4,8}.0^{15,20}]henicosa-1(21),2(10),3,8,13,15,17,19-octaen-16-yl)oxy]propyl]triazol-4-yl]methoxy]benzenesulfonamide, ... (4 entities in total) |
| Functional Keywords | drug-dna complex, telomeric g-quadruplex, dna |
| Biological source | Homo sapiens |
| Total number of polymer chains | 1 |
| Total formula weight | 8638.31 |
| Authors | Bazzicalupi, C.,Gratteri, P.,Petreni, A.,Nocentini, A. (deposition date: 2021-09-07, release date: 2022-09-21, Last modification date: 2024-07-24) |
| Primary citation | Nocentini, A.,Di Porzio, A.,Bonardi, A.,Bazzicalupi, C.,Petreni, A.,Biver, T.,Bua, S.,Marzano, S.,Amato, J.,Pagano, B.,Iaccarino, N.,De Tito, S.,Amente, S.,Supuran, C.T.,Randazzo, A.,Gratteri, P. Development of a multi-targeted chemotherapeutic approach based on G-quadruplex stabilisation and carbonic anhydrase inhibition. J Enzyme Inhib Med Chem, 39:2366236-2366236, 2024 Cited by PubMed Abstract: A novel class of compounds designed to hit two anti-tumour targets, G-quadruplex structures and human carbonic anhydrases (hCAs) IX and XII is proposed. The induction/stabilisation of G-quadruplex structures by small molecules has emerged as an anticancer strategy, disrupting telomere maintenance and reducing oncogene expression. hCAs IX and XII are well-established anti-tumour targets, upregulated in many hypoxic tumours and contributing to metastasis. The ligands reported feature a berberine G-quadruplex stabiliser scaffold connected to a moiety inhibiting hCAs IX and XII. experiments showed that our compounds selectively stabilise G-quadruplex structures and inhibit hCAs IX and XII. The crystal structure of a telomeric G-quadruplex in complex with one of these ligands was obtained, shedding light on the ligand/target interaction mode. The most promising ligands showed significant cytotoxicity against CA IX-positive HeLa cancer cells in hypoxia, and the ability to stabilise G-quadruplexes within tumour cells. PubMed: 38905127DOI: 10.1080/14756366.2024.2366236 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.83 Å) |
Structure validation
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