 |
Journal articles
Beyond the Rule of 5: Impact of PEGylation with Various Polymer Sizes on Pharmacokinetic Properties, Structure–Properties Relationships of mPEGylated Small Agonists of TGR5 Receptor
Vanessa Hoguet
1
Manuel Lasalle
1
Mathieu Maingot
1
Geoffroy Dequirez
1
Rajaa Boulahjar
1
Florence Leroux
1
Catherine Piveteau
1
Adrien Herledan
1
Alexandre Biela
1
Julie Dumont
1
Oscar Chávez-Talavera
2
Loïc Belloy
2
Isabelle Duplan
2
Nathalie Hennuyer
2
Laura Butruille
2
Sophie Lestavel
2
Emmanuel Sevin
3
Maxime Culot
3
Fabien Gosselet
3
Bart Staels
2
Benoit Deprez
1, *
Anne Tailleux
2
Julie Charton
1, *
Rajaa Boulahjar 1
Author
Florence Leroux 1
Author
Catherine Piveteau 1
Author
Adrien Herledan 1
Author
Isabelle Duplan 2
Author
Nathalie Hennuyer 2
Author
Laura Butruille 2
Author
Sophie Lestavel 2
Author IdHAL : sophie-lestavel
Emmanuel Sevin 3
Author
Maxime Culot 3
Author IdHAL : maxime-culot ORCID : https://orcid.org/0000-0001-7452-0867
Fabien Gosselet 3
Author IdHAL : fabgoss ORCID : https://orcid.org/0000-0002-0481-5026
Bart Staels 2
Author IdHAL : bart-staels ResearcherId : http://www.researcherid.com/rid/N-9497-2016 ORCID : https://orcid.org/0000-0002-3784-1503
1
M2SV - Médicaments et molécules pour agir sur les Systèmes Vivants - U 1177 (- Faculté de pharmacie de Lille
- 3 rue du Pr Laguesse
- F-59000 Lille - France)
- Institut Pasteur de Lille (1 Rue du Professeur Calmette - Lille Cedex - 59019 - France)
- RIIP - Réseau International des Instituts Pasteur (25, rue du Dr Roux 75724 Paris Cedex 15 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1177 (101, rue de Tolbiac, 75013 Paris - France)
- Université de Lille : UMRS761 (Lille - France)
2
RNMCD - U1011 - Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires (1 rue du Prof Calmette - 59019 LILLE Cedex - France)
- Institut Pasteur de Lille (1 Rue du Professeur Calmette - Lille Cedex - 59019 - France)
- RIIP - Réseau International des Instituts Pasteur (25, rue du Dr Roux 75724 Paris Cedex 15 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1011 (101, rue de Tolbiac, 75013 Paris - France)
- Université de Lille : U1011 (Lille - France)
- CHRU Lille - Centre Hospitalier Régional Universitaire [Lille] (2, avenue Oscar Lambret - 59037 Lille Cedex - France)
3
LBHE - Laboratoire de la Barrière Hémato-Encéphalique (Faculté Jean Perrin, Rue Jean Souvraz, 62300 LENS - France)
- UA - Université d'Artois : UR2465 (9 rue du Temple - BP 10665 - 62030 Arras cedex - France)
Abstract : PEGylation of therapeutic agents is known to improve the pharmacokinetic behavior of macromolecular drugs and nanoparticles. In this work, we performed the conjugation of polyethylene glycols (220-5000 Da) to a series of non-steroidal small agonists of the bile acids receptor TGR5. A suitable anchoring position on the agonist was identified to retain full agonistic potency with the conjugates. We describe herein an extensive structure-properties relationships study allowing us to finely describe the non-linear effects of the PEG length on the physicochemical as well as the in vitro and in vivo pharmacokinetic properties of these compounds. When appending a PEG of suitable length to the TGR5 pharmacophore, we were able to identify either systemic or gut lumen-restricted TGR5 agonists.
Document type :
Journal articles
Domain :
Complete list of metadata
https://hal-univ-artois.archives-ouvertes.fr/hal-03185533
Contributor : Virginie Justin-Labonne <>
Submitted on : Tuesday, March 30, 2021 - 1:48:46 PM
Last modification on : Monday, July 19, 2021 - 2:06:03 PM
Contributor : Virginie Justin-Labonne <>
Submitted on : Tuesday, March 30, 2021 - 1:48:46 PM
Last modification on : Monday, July 19, 2021 - 2:06:03 PM
Identifiers
- HAL Id : hal-03185533, version 1
- DOI : 10.1021/acs.jmedchem.0c01774
- PUBMED : 33470812
Collections
UNIV-ARTOIS | RIIP | UNIV-LILLE | LBHE | RIIP_LILLE | RNMCD
Citation
Vanessa Hoguet, Manuel Lasalle, Mathieu Maingot, Geoffroy Dequirez, Rajaa Boulahjar, et al.. Beyond the Rule of 5: Impact of PEGylation with Various Polymer Sizes on Pharmacokinetic Properties, Structure–Properties Relationships of mPEGylated Small Agonists of TGR5 Receptor. Journal of Medicinal Chemistry, American Chemical Society, 2021, 64 (3), pp.1593-1610. ⟨10.1021/acs.jmedchem.0c01774⟩. ⟨hal-03185533⟩
Metrics
Record views