Selective Removal of Denatured Proteins Using MOF Nanopores

Here we present, for the first time, the selective adsorption of denatured proteins using a metal–organic framework (MOF), demonstrating promising potential for protein purification. Typical proteins, such as lysozyme and carbonic anhydrase B, enter the pores of MIL-101 through their narrow apertures when they are denatured to an unfolded state. Selective adsorption is achieved by finely tuning two key features: the sizes of the aperture and cage of the MOF nanopores, which are responsible for sorting unfolded polypeptide chains and inhibiting the translocation of the native form into the pores, respectively. By leveraging this selective adsorption, we successfully purified a mixture of native and denatured proteins by adding MOF to the mixture, achieving a native purity of over 99%.