Vorherr, Thomas, Lewis, Ian, Berghausen, Joerg, Huth, Felix, Schaefer, Michael, Wille, Roman Mariano, Gao, Jinhai and Wang, Bing (2019) Pyridyl-Ala modified cyclic hexapeptides: in-vitro and in-vivo profiling for oral bioavailability. International journal of peptide research and therapeutics., 19 (4). pp. 275-380. ISSN 1573-3149

Abstract

We and others have been aiming at modifications to maintain or to enhance solubility while enabling permeability for cyclic hexapeptides. Especially, the 2-pyridyl-Ala modification was investigated, since in this case, the pyridyl-nitrogen is able to form an H-bond to the NH of the same residue. The hypothesis of a backbone side-chain interaction was demonstrated by NMR experiments, and further results obtained on a variety of pyridyl-Ala derivatives, studied systematically in the context of permeability, are presented in this contribution. Thus, this study sheds some more light on the pyridyl-Ala modification, which had been reported earlier. In addition to the in-vitro profiling, the extent of oral bioavailability was assessed in rats. In principle, the pyridyl-Ala residue can be considered as an amino acid supporting oral uptake.

Item Type:	Article
Keywords:	Conformation, cyclic peptide, oral bioavailability, permeability, pharmacokinetics
Date Deposited:	09 Nov 2019 00:45
Last Modified:	09 Nov 2019 00:45
URI:	https://oak.novartis.com/id/eprint/39684