Efficient solid-phase synthesis of a series of cyclic and linear peptoid-dexamethasone conjugates for the cell permeability studies.
Cyclic peptides and their cyclic analogs have received a great deal of attention because of their numerous interesting biological activities and their challenging chemical synthesis. It has also been hypothesized that they might improve the cell permeability compared to linear molecules by providing internal hydrogen bonding and generally decreasing the conformational flexibility. In this study, a series of cyclic and linear peptoid-dexamethasone conjugates were rationally designed and efficiently synthesized on solid-phase for systematic cell permeability studies using reporter gene-based assays. These model compounds should be used to reveal how the cell permeability of cyclic molecules is affected by several physicochemical properties, especially, the reduced conformational flexibility and the ring size. In addition, the synthetic strategy that was adopted in this study can also provide a robust platform for postchemical modifications of various molecular scaffolds in solid-phase or solution-phase syntheses.
Cho
Suekyung
S
Department of Chemistry and Nano Science, Ewha Womans University, Seoul 120-750, South Korea.
Choi
Jiyoung
J
Kim
Arim
A
Lee
Yunyoung
Y
Kwon
Yong-Uk
YU
D000595:Amino Acid Sequence; D002463:Cell Membrane Permeability / Q000187:drug effects* / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D003907:Dexamethasone / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006860:Hydrogen Bonding; D008872:Microwaves; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D034444:Peptoids / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D010456:Peptides, Cyclic; D034444:Peptoids; D003907:Dexamethasone