PubMed · 1984149
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L Smith. 1991-01-09. Chymopapain.. https://pubmed.ncbi.nlm.nih.gov/1984149/
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We studied the effect of three electrolytes (LiCl, Na(2)SO(4), GuHCl) on the unfolding reaction of chymopapain, a two-domain protein belonging in the papain family of cysteine proteinases. Due to methodological reasons, these studies were carried out at pH 1.5 where the protein unfolds following biphasic kinetics. We have observed the presence of two different effects of electrolyte concentration on the unfolding reactions. At low ionic strength, the ionic atmosphere brought about an increase in reaction rates, regardless of the type of ions being present; this effect is attributed to a general "electrostatic screening" of charge-charge interactions in the macromolecule. At high ionic strength, each electrolyte exerted a distinctively different effect: both rate constants were largely increased by GuHCl (a well-known protein denaturant), but only slightly by LiCl; in contrast, Na(2)SO(4) (a good precipitant) decreased the value of both unfolding rates. These ion-specific (Hofmeister) effects were further used to estimate changes in accessible surface area (DeltaASA) upon formation of the transition states (TS) for unfolding. Results obtained with LiCl and Na(2)SO(4), which we analyzed by means of a parameterization derived from published solubility data of amino acid derivatives, are consistent with DeltaASA increments (for each phase) of about 8.0% of the total theoretical DeltaASA for complete unfolding of the chymopapain molecule. Results in the presence of GuHCl, which were analyzed by using a previous parameterization of protein unfolding data, gave larger DeltaASAs of activation, equivalent to 13 and 16% of the total unfolding DeltaASA.
Since the first injection of chymopapain in 1963, percutaneous intradiscal therapies have been used to treat discogenic back and leg pain. The percutaneous discectomy techniques treat contained disc herniations not by resecting the prolapsed disc material but rather through central decompression of the disc. By removing a small volume of tissue from the disc nucleus, a large reduction in overall disc pressure is achieved with consequent relief of neural compression. DISC Nucleoplasty and Dekompressor are the two leading percutaneous discectomy technologies currently. Although rigorous clinical testing of their efficacy is ongoing, there has now been a 40-year history confirming the concept of percutaneous disc decompression, and initial results are very promising. Discogenic low back pain can also arise from annular tears and other forms of internal disc derangement (IDD). Annuloplasty techniques, such as IntraDiscal Electrothermal Therapy (IDET) and discTRODE, have been developed over the past decade that thermally treat the lesions of IDD. Although the therapeutic mechanisms of thermal annuloplasty have yet to be fully elucidated, research studies demonstrate that the procedure can be effective for appropriately selected patients with degenerative disc disease characterized by discographically proven painful annular fissures. Other novel intradiscal therapies are emerging for percutaneous treatment of discogenic pain and await more widespread clinical evaluation.
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