| Added by | celine.gongora |
|---|---|
| Group name | EquipeCG |
| Item Type | Journal Article |
| Title | Carboxylate-functionalized foldamer inhibitors of HIV-1 integrase and Topoisomerase 1: artificial analogues of DNA mimic proteins |
| Creator | Corvaglia et al. |
| Author | Valentina Corvaglia |
| Author | Daniel Carbajo |
| Author | Panchami Prabhakaran |
| Author | Krzysztof Ziach |
| Author | Pradeep Kumar Mandal |
| Author | Victor Dos Santos |
| Author | Carole Legeay |
| Author | Rachel Vogel |
| Author | Vincent Parissi |
| Author | Philippe Pourquier |
| Author | Ivan Huc |
| Abstract | Inspired by DNA mimic proteins, we have introduced aromatic foldamers bearing phosphonate groups as synthetic mimics of the charge surface of B-DNA and competitive inhibitors of some therapeutically relevant DNA-binding enzymes: the human DNA Topoisomerase 1 (Top1) and the human HIV-1 integrase (HIV-1 IN). We now report on variants of these anionic foldamers bearing carboxylates instead of phosphonates. Several new monomers have been synthesized with protecting groups suitable for solid phase synthesis (SPS). Six hexadecaamides have been prepared using SPS. Proof of their resemblance to B-DNA was brought by the first crystal structure of one of these DNA-mimic foldamers in its polyanionic form. While some of the foldamers were found to be as active as, or even more active than, the original phosphonate oligomers, others had no activity at all or could even stimulate enzyme activity in vitro. Some foldamers were found to have differential inhibitory effects on the two enzymes. These results demonstrate a strong dependence of inhibitory activity on foldamer structure and charge distribution. They open broad avenues for the development of new classes of derivatives that could inhibit the interaction of specific proteins with their DNA target thereby influencing the cellular pathways in which they are involved. |
| Publication | Nucleic Acids Research |
| Date | May 10, 2019 |
| Journal Abbr | Nucleic Acids Res. |
| Language | eng |
| DOI | 10.1093/nar/gkz352 |
| ISSN | 1362-4962 |
| Short Title | Carboxylate-functionalized foldamer inhibitors of HIV-1 integrase and Topoisomerase 1 |
| Library Catalog | PubMed |
| Extra | PMID: 31073604 |
| Tags | ERC, original, top |
| Date Added | 2019/05/14 - 11:50:54 |
| Date Modified | 2019/11/27 - 11:30:50 |
| Notes and Attachments | PubMed entry (Attachment) |
Institut de Recherche en Cancérologie de
