Crowning Proteins: Modulating the Protein Surface Properties using Crown Ethers**

Lee, Cheng-Chung; Maestre-Reyna, Manuel; Hsu, Kai-Cheng; Wang, Hao-Ching; Liu, Chia-I; Jeng, Wen-Yih; Lin, Li-Ling; Wood, Richard; Chou, Chia-Cheng; Yang, Jinn-Moon; Wang, Andrew H-J

Crown ethers are small, cyclic polyethers that have found wide-spread use in phase-transfer catalysis and, to a certain degree, in protein chemistry. Crown ethers readily bind metallic and organic cations, including positively charged amino acid side chains. We elucidated the crystal structures of several protein-crown ether co-crystals grown in the presence of 18-crown-6. We then employed biophysical methods and molecular dynamics simulations to compare these complexes with the corresponding apoproteins and with similar complexes with ring-shaped low-molecular-weight polyethylene glycols. Our studies show that crown ethers can modify protein surface behavior dramatically by stabilizing either intra- or intermolecular interactions. Consequently, we propose that crown ethers can be used to modulate a wide variety of protein surface behaviors, such as oligomerization, domain–domain interactions, stabilization in organic solvents, and crystallization.