PEGylated leuprolide with improved pharmacokinetic properties.
Leuprolide
PEGylation
Pharmacokinetics
Journal
Bioorganic & medicinal chemistry
ISSN: 1464-3391
Titre abrégé: Bioorg Med Chem
Pays: England
ID NLM: 9413298
Informations de publication
Date de publication:
15 02 2020
15 02 2020
Historique:
received:
17
11
2019
revised:
26
12
2019
accepted:
02
01
2020
pubmed:
14
1
2020
medline:
7
2
2021
entrez:
14
1
2020
Statut:
ppublish
Résumé
Leuprolide, a gonadotropin-releasing hormone (GnRH) agonist widely used in androgen deprivation therapy for the treatment of advanced prostate cancer, suffers from a short circulating half-life like other peptide therapeutics. As an attempt to improve its pharmacokinetic properties, two PEGylated leuprolides with different molecular weight were synthesized utilizing N-hydroxysuccinimidyl (NHS) conjugation chemistry. The reaction conditions, including reaction temperature, reaction time and feed ratio of the reactants, were optimized to obtain a higher yield. Reverse-phase high performance liquid chromatography (RP-HPLC) characterization indicates a high purity of the resulting conjugates. Matrix-assisted laser desorption mass spectrometry (MALDI-MS) characterization suggests a 1:1 PEGylation.
Identifiants
pubmed: 31926774
pii: S0968-0896(19)31932-7
doi: 10.1016/j.bmc.2020.115306
pii:
doi:
Substances chimiques
Polyethylene Glycols
3WJQ0SDW1A
Leuprolide
EFY6W0M8TG
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
115306Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.