title: Optimizing PK properties of cyclic peptides: the effect of side chain substitutions on permeability and clearance().
abstract: A series of cyclic peptides were designed and prepared to investigate the physicochemical properties that affect oral bioavailabilty of this chemotype in rats. In particular, the ionization state of the peptide was examined by the incorporation of naturally occurring amino acid residues that are charged in differing regions of the gut. In addition, data was generated in a variety of in vitro assays and the usefulness of this data in predicting the subsequent oral bioavailability observed in the rat is discussed.
authors.affiliation: Department of Chemistry, University of California Santa Cruz, California, USA.
authors.forename: Arthur C
authors.initials: AC
authors.lastname: Rand
authors.forename: Siegfried S F
authors.initials: SS
authors.lastname: Leung
authors.forename: Heather
authors.initials: H
authors.lastname: Eng
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Rotter
authors.forename: Raman
authors.initials: R
authors.lastname: Sharma
authors.forename: Amit S
authors.initials: AS
authors.lastname: Kalgutkar
authors.forename: Yizhong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Manthena V
authors.initials: MV
authors.lastname: Varma
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Farley
authors.forename: Bhagyashree
authors.initials: B
authors.lastname: Khunte
authors.forename: Chris
authors.initials: C
authors.lastname: Limberakis
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.forename: Spiros
authors.initials: S
authors.lastname: Liras
authors.forename: Alan M
authors.initials: AM
authors.lastname: Mathiowetz
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Jacobson
authors.forename: R Scott
authors.initials: RS
authors.lastname: Lokey