The synthesis of a geminally perfluoro-tert-butylated beta-amino acid and its protected forms as a potential pharmacokinetic modulator and reporter for peptide-based pharmaceuticals.
To modulate and report the pharmacokinetics of peptide-based pharmaceuticals, a novel geminally perfluoro-tert-butylated beta-amino acid (betaFa) and its Fmoc- and Boc-protected forms were designed and synthesized. betaFa was incorporated into a model tripeptide via standard solid-phase chemistry. Both the amino acid (free and protected) and the tripeptide show a sharp singlet 19F NMR signal. Reversed-phase chromatography and 1-octanol/water partition measurements demonstrate that betaFa is extremely hydrophobic.
Jiang
Zhong-Xing
ZX
Department of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, University of Utah, Salt Lake City, Utah 84112, USA.
Yu
Y Bruce
YB
D005466:Fluorocarbons / Q000737:chemistry*; D010455:Peptides / Q000032:analysis* / Q000493:pharmacokinetics*; D011487:Protein Conformation
D005466:Fluorocarbons; D010455:Peptides