Design, synthesis and structure-activity relationship of new arginine vasopressin analogues containing proline derivatives in position 2

Anna Kwiatkowska , Monika Lewandowska , Lenka Borovičková , Jiřina Slaninová , Bernard Lammek , Adam Prahl

Abstract

In this study, we present the synthesis and pharmacological properties of new analogues of arginine vasopressin modified in the N‐terminal part of the molecule with proline derivatives: indoline‐2‐carboxylic acid (Ica) and (2S,4R)‐4‐(naphthalene‐2‐ylmethyl)pyrrolidine‐2‐carboxylic acid. All the peptides were tested for pressor, antidiuretic and in vitro uterotonic activities. We also determined their binding affinity to the human oxytocin receptor. The Ica2 substitution resulted in two moderately potent and selective antioxytocic agents: [Mpa1, Ica2, D‐Arg8]VP and [Mpa1,Ica2,Val4,D‐Arg8]VP (pA2 = 7.09 and 7.50, respectively). On the other hand, peptides modified with (2S,4R)‐4‐(naphthalene‐2‐ylmethyl)pyrrolidine‐2‐carboxylic acid, apart from their moderate antioxytocic activity, turned out to be weak antagonists of the pressor response to arginine vasopressin. The results of this study provide useful information about the structure–activity relationship of arginine vasopressin analogues and can help to design compounds with desired biological properties.
Author Anna Kwiatkowska (FCh / DOCh)
Anna Kwiatkowska,,
- Department of Organic Chemistry
, Monika Lewandowska (FCh / DOCh / LChB)
Monika Lewandowska,,
- Laboratory of Chemistry of Biopolymers
, Lenka Borovičková
Lenka Borovičková,,
-
, Jiřina Slaninová
Jiřina Slaninová,,
-
, Bernard Lammek (FCh / DOCh / LChB)
Bernard Lammek,,
- Laboratory of Chemistry of Biopolymers
, Adam Prahl (FCh / DOCh / LChB)
Adam Prahl,,
- Laboratory of Chemistry of Biopolymers
Journal seriesChemical Biology & Drug Design, ISSN 1747-0277, e-ISSN 1747-0285, (A 25 pkt)
Issue year2013
Vol81
No3
Pages420-428
Publication size in sheets0.5
Keywords in Englishantidiuretic hormone, arginine vasopressin, binding affinity to OTR, conformational restriction, proline derivatives
DOIDOI:10.1111/cbdd.12093
URL https://doi.org/10.1111/cbdd.12093
Languageen angielski
Score (nominal)25
ScoreMinisterial score = 25.0, 08-06-2018, ArticleFromJournal
Ministerial score (2013-2016) = 25.0, 08-06-2018, ArticleFromJournal
Publication indicators WoS Impact Factor: 2013 = 2.507 (2) - 2013=2.479 (5)
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