Synthesis and Stereochemical Assignment of Conioidine A: DNA- and HSA-Binding Studies of the Four Diastereomers

Abstract

Conioidine A (1), isolated in 1993 with unknown relative and absolute configuration, was suggested to be a DNA-binding compound by an indirect technique. Four stereoisomers of conioidine A have been synthesized from D-and L-proline, and the natural product has been identified as possessing (4R,6R) absolute configuration. Binding of the conioidine diastereomers to calf thymus DNA (CT DNA) and human serum albumin (HSA) has been investigated by fluorescence spectroscopy and isothermal titration calorimetry (ITC). All stereoisomers display at least an order of magnitude weaker binding to DNA than the control compound netropsin; however, a strong association with HSA was observed for the (4R,6S) stereoisomer.

Noncovalent interactions of antitumor cycloplatinated complexes containing trifluoroacetate ligands as the leaving group with bovine serum albumin. Implications for drug design

“…There are two negative signals at 222 and 208 nm in the CD spectra, which clearly indicate the existence of the ahelical structure of SA proteins. 67,71 Fig. 7 shows a decrease of ellipticity of pure BSA upon the addition of cycloplatinated complexes implying that 1 and 2 induced conformational alteration of pure proteins and reduced significantly the content of a-helical secondary structures.…”

“…There are two negative signals at 222 and 208 nm in the CD spectra, which clearly indicate the existence of the α-helical structure of SA proteins. 67,71…”