PMID- 31073604
OWN - NLM
STAT- MEDLINE
DCOM- 20191125
LR  - 20200309
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Print)
IS  - 0305-1048 (Linking)
VI  - 47
IP  - 11
DP  - 2019 Jun 20
TI  - Carboxylate-functionalized foldamer inhibitors of HIV-1 integrase and 
      Topoisomerase 1: artificial analogues of DNA mimic proteins.
PG  - 5511-5521
LID - 10.1093/nar/gkz352 [doi]
AB  - 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.
CI  - (c) The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic 
      Acids Research.
FAU - Corvaglia, Valentina
AU  - Corvaglia V
AD  - Department of Pharmacy and Center for Integrated Protein Science, 
      Ludwig-Maximilians-Universitat, Munchen 81377, Germany.
AD  - Universite de Bordeaux, CNRS, Bordeaux Institut National Polytechnique, CBMN (UMR 
      5248), Institut Europeen de Chimie et Biologie, Pessac 33600, France.
FAU - Carbajo, Daniel
AU  - Carbajo D
AD  - Universite de Bordeaux, CNRS, Bordeaux Institut National Polytechnique, CBMN (UMR 
      5248), Institut Europeen de Chimie et Biologie, Pessac 33600, France.
FAU - Prabhakaran, Panchami
AU  - Prabhakaran P
AD  - Universite de Bordeaux, CNRS, Bordeaux Institut National Polytechnique, CBMN (UMR 
      5248), Institut Europeen de Chimie et Biologie, Pessac 33600, France.
FAU - Ziach, Krzysztof
AU  - Ziach K
AD  - Universite de Bordeaux, CNRS, Bordeaux Institut National Polytechnique, CBMN (UMR 
      5248), Institut Europeen de Chimie et Biologie, Pessac 33600, France.
FAU - Mandal, Pradeep Kumar
AU  - Mandal PK
AD  - Department of Pharmacy and Center for Integrated Protein Science, 
      Ludwig-Maximilians-Universitat, Munchen 81377, Germany.
AD  - Universite de Bordeaux, CNRS, Bordeaux Institut National Polytechnique, CBMN (UMR 
      5248), Institut Europeen de Chimie et Biologie, Pessac 33600, France.
FAU - Santos, Victor Dos
AU  - Santos VD
AD  - Sanofi recherche & developpement, Montpellier 34184, France.
FAU - Legeay, Carole
AU  - Legeay C
AD  - Sanofi recherche & developpement, Montpellier 34184, France.
FAU - Vogel, Rachel
AU  - Vogel R
AD  - Sanofi recherche & developpement, Montpellier 34184, France.
FAU - Parissi, Vincent
AU  - Parissi V
AD  - Universite de Bordeaux, CNRS, Laboratoire de Microbiologie Fondamentale et 
      Pathogenicite (UMR 5234), Bordeaux 33146, France.
FAU - Pourquier, Philippe
AU  - Pourquier P
AD  - INSERM U1194, Institut de Recherche en Cancerologie de Montpellier & Universite 
      de Montpellier, Montpellier 34298, France.
FAU - Huc, Ivan
AU  - Huc I
AD  - Department of Pharmacy and Center for Integrated Protein Science, 
      Ludwig-Maximilians-Universitat, Munchen 81377, Germany.
AD  - Universite de Bordeaux, CNRS, Bordeaux Institut National Polytechnique, CBMN (UMR 
      5248), Institut Europeen de Chimie et Biologie, Pessac 33600, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 0 (Amides)
RN  - 0 (DNA, B-Form)
RN  - 0 (HIV Integrase Inhibitors)
RN  - EC 2.7.7.- (HIV Integrase)
RN  - EC 5.99.1.2 (DNA Topoisomerases, Type I)
RN  - EC 5.99.1.2 (TOP1 protein, human)
SB  - IM
MH  - Amides/*chemistry
MH  - Biocatalysis
MH  - Biomimetic Materials/chemistry
MH  - Crystallography, X-Ray
MH  - DNA Topoisomerases, Type I/*chemistry
MH  - DNA, B-Form/*chemistry
MH  - HIV Integrase/*chemistry
MH  - HIV Integrase Inhibitors/chemical synthesis/*chemistry
MH  - HIV-1/enzymology
MH  - Humans
MH  - Molecular Structure
MH  - Protein Conformation
MH  - Solid-Phase Synthesis Techniques
PMC - PMC6582331
EDAT- 2019/05/11 06:00
MHDA- 2019/11/26 06:00
PMCR- 2019/05/10
CRDT- 2019/05/11 06:00
PHST- 2019/04/26 00:00 [accepted]
PHST- 2019/04/21 00:00 [revised]
PHST- 2019/03/05 00:00 [received]
PHST- 2019/05/11 06:00 [pubmed]
PHST- 2019/11/26 06:00 [medline]
PHST- 2019/05/11 06:00 [entrez]
PHST- 2019/05/10 00:00 [pmc-release]
AID - 5487674 [pii]
AID - gkz352 [pii]
AID - 10.1093/nar/gkz352 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 2019 Jun 20;47(11):5511-5521. doi: 10.1093/nar/gkz352.