β-Biguanidinium-cyclodextrin: a supramolecular mimic of mitochondrial ADP/ATP carrier protein

We reported a novel mono-β-cyclodextrin derivative, mono-6-deoxy-6-biguanidino-β-cyclodextrin (β-biGCD), which was investigated as a mimic of ADP/ATP carrier (AAC). Its affinity toward AMP, ADP, and ATP was evaluated by means of isothermal titration calorimetry (ITC). The association constants (Ka) of β-biGCD binding to AMP, ADP, and ATP were determined to be (1.07±0.04)×106, (5.86±0.02)×106, and (4.33±0.06)×106 L mol−1, respectively, which were 100-fold higher than mono-guanidino-β-cyclodextrin (ca. 104 L mol−1). UV spectroscopic titrations further confirmed the above results. The interaction between β-biGCD and nucleotides was probed by docking simulation. These results reveal that the biguanidinium moiety mimics the arginine residues of mitochondrial AAC protein.

Graphical abstractDownload high-res image (265KB)Download full-size imageModified β-cyclodextrin with a cationic biguanidyl group exhibits high binding affinity toward AMP, ADP, and ATP in water, which mimic the function of mitochondria ADP/ATP carrier protein (AAC). The cationic biguanidyl group plays a role analogue to the Arg residues of mitochondrial AAC.