The invention relates to peptoid reagents that interact preferentially with a pathogenic form of a conformational disease protein as compared to a nonpathogenic form of the conformational disease protein where the peptoid reagent comprises an amino-terminal region, a carboxy-terminal region, and at least one peptoid region between the amino-terminal region and the carboxy-terminal region where the peptoid region comprises 3 to about 30 N-substituted glycines, and optionally one or more amino acids. The invention also relates to methods of using the peptoids in detecting and isolating prions, and in the treatment and prevention of prion-related diseases.