PMSF (Synonyms: Benzylsulfonyl fluoride, NSC 88499, PMSF)

PMSF (Phenylmethanesulfonyl fluoride) is an irreversible serine/cysteine protease inhibitor and PMSF commonly used in the preparation of cell lysates ^[1,2]. phenylmethylsulfonyl fluoride (PMSF) is also an inhibitor of fatty acid amide hydrolase (FAAH) ^[3].

Aqueous preparations of PMSF become inactive toward proteases unless promptly brought into contact with protease. Inactivation of PMSF increases with increased pH and temperature. Half-lives of the inhibitor at 25°C are approximately 110,55, and 35 min at pH 7.0, 7.5, and 8.0, respectively. At pH 8, 100 μM PMSF is almost completely inactivated within 1 hr at 25°C or within 22 hr at 4°C. Stock solutions of PMSF in 100% isopropanol are stable at 25°C for months if not longer. Reactivation of PMSF-inhibited chymotrypsin did not occur within 1 week at 25°C at pH 7.0 ^[4]. PMSF inhibits the acylation of the inositol residue of GPI intermediates in bloodstream form T. brucei. PMSF inhihits the formntion of glycolipid C but does not inhibit fatty acid remodeling in vitro. PMSF inhihits GPI acylation and ethanolamine phosphatp addition in procyclic trypanosomes but not in Hela cells ^[5].

PMSF has a notable antinociceptive effect at doses 120 and 300 mg/kg. The dose of (60 mg/kg, i.p.) PMSF was considered as a sub-antinociceptive dose. A sub-antinociceptive dose (60 mg/kg) of PMSF could reduce tolerance in both acute and chronic methods of administration. However, alleviation of dependence and suppression of oxidative stress markers occurred in the chronic administration of PMSF ^[3].

References:
[1]. Tunlid A, Jansson S. Proteases and their involvement in the infection and immobilization of nematodes by the nematophagous fungus Arthrobotrys oligospora[J]. Applied and Environmental Microbiology, 1991, 57(10): 2868-2872.
[2]. Rajakumar A, Brandon H M, Daftary A, et al. Evidence for the functional activity of hypoxia-inducible transcription factors overexpressed in preeclamptic placentae[J]. Placenta, 2004, 25(10): 763-769.
[3]. Akbarabadi E A, Vardanjani H R, Molavinia S, et al. PMSF Attenuates Morphine Antinociceptive Tolerance and Dependence in Mice: Its Association with the Oxidative Stress Suppression[J]. Iranian Journal of Pharmaceutical Research: IJPR, 2021, 20(3): 300.
[4]. James G T. Inactivation of the protease inhibitor phenylmethylsulfonyl fluoride in buffers[J]. Analytical biochemistry, 1978, 86(2): 574-579.
[5]. Güther M L, Masterson W J, Ferguson M A. The effects of phenylmethylsulfonyl fluoride on inositol-acylation and fatty acid remodeling in African trypanosomes[J]. Journal of Biological Chemistry, 1994, 269(28): 18694-18701.