Perchlorate-induced denaturation of ribonuclease A: investigation of possible folding intermediates.

Perchlorate-denatured ribonuclease A (PDR) is known to show a circular dichroism (CD) spectrum suggestive of substantial secondary structure. Thus, PDR may be a molten globule form of ribonuclease A. We find that any secondary structure present in PDR does not provide measurable protection against amide proton exchange, and PDR does not belong to the class of structured molten globules. CD spectra of short peptides show that the perchlorate anion affects these spectra in a way that could be mistaken for secondary structure formation; thus, caution must be used in interpreting CD spectra of peptides and proteins taken in perchlorate solutions.