Bioorganic & Medicinal Chemistry 26 (2018) 3039–3045 Contents lists available at ScienceDirect Bioorganic & Medicinal Chemistry journal homepage: www.elsevier.com/locate/bmc Building bridges for highly selective, potent and stable oxytocin and vasopressin analogs a b b b b Rhiannon Beard , Andy Stucki , Muriel Schmitt , Gabrielle Py , Christophe Grundschober , c a,⇑ Antony D. Gee , Edward W. Tate Department of Chemistry, Imperial College London, Exhibition Road, London SW7 2AZ, UK Roche Pharma Research and Early Development, Discovery Neuroscience, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland Division of Imaging Sciences, King’s College London, 4th Floor, Lambeth Wing, St Thomas’ Hospital, SE1 7EH London, UK article i nfo abstract Article history: Oxytocin (OT) is an exciting potential therapeutic agent, but it is highly sensitive to modiﬁcation and suf- Received 28 January 2018 fers extensive degradation at elevated temperature and in vivo. Here we report studies towards OT ana- Revised 9 March 2018 logs with favorable selectivity, afﬁnity and potency towards the oxytocin receptor (OTR), in addition to Accepted 10 March 2018 improving stability of the peptide by bridging the disulﬁde region with substituted dibromo-xylene ana- Available online 12 March 2018 logs. We found
Bioorganic & Medicinal Chemistry – Elsevier
Published: Jul 15, 2018
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