Cytomegalovirus protease

Darke PL, Cole JL, Waxman L, Hall DL, Sardana MK, Kuo LC (1996) Active human cytomegalovirus protease is a dimer. J Biol Chem 271 7445-7449 De Francesco R, Carfi A (2007) Advances in the development of new therapeutic agents targeting the NS3 A serine protease or the NS5B RNA-dependent RNA polymerase of the hepatitis C virus. Adv Drug Deliv Rev 59 1242-1262... 

Margosiak SA, Vanderpool DL, Sisson W, Pinko C, Kan CC (1996) Dimerization of the human cytomegalovirus protease kinetic and biochemical characterization of the catalytic homodimer. Biochemistry 35 5300-5307... 

Tong L, Qian C, Massariol MJ, Bonneau PR, Cordingley MG, Lagace L (1996) A new serine-protease fold revealed by the crystal structure of human cytomegalovirus protease. Nature 383 272-275... 

Table 2.5 Mole ratios for titration of DBQ drug (D) and cytomegalovirus protease A144L (P) during incubation (Reaction) and after passing through a GPC spin column (Coeluted).

M. O. Palmier, R. C. Wiegand, B. C. Holwerda, W. C. Stallings Three-dimensional structure of human cytomegalovirus protease, Nature 1996, 383, 279-282. 

B. Hellmig, S. S. Hoog, C. A. Janson, W. W. Smith, S. S. Abdel-Meguid Unique fold and active site in cytomegalovirus protease, Nature 1996, 383, 275-279. 

Structure of the human cytomegalovirus protease catalytic domain reveals a novel serine protease fold and catalytic triad, Cdl 1996, 86, 835-843. 

Siegel, M.M., Tabei, K., Bebemitz, G.A., Baum, F.Z. Rapid methods for screening low molecular mass compounds non-covalently bound to proteins using size exclusion and mass spectrometry applied to inhibitors of human cytomegalovirus proteases. J. Mass Spectrom. 1998, 33, 264-273. 

Veinberg G, Vorona M, Shestakova I, Kanepe I, Lukevics E (2003) Some of the more notable advances concern the development of mechanism-based serine protease inhibitors of elastase, cytomegalovirus protease, thrombin, prostate specific antigen, and cell metastasis and as inhibitors of acyl-CoA cholesterol acyl transferase. Curr Med Chem 10 1741... 

Very recently, (3-lactam antibiotics have been shown to offer neuroprotection by increasing glutamate transporters expression via gene activation [15] in addition, the discoveries of new biologically active (3-lactams such as cholesterol acyl transferase inhibitors [16-18], thrombin inhibitors [19], human cytomegalovirus protease inhibitors [20], matrix-metallo protease inhibitors [21], inhibitors of human leukocyte elastase (HLE) [22, 23] and cysteine protease [24, 25], and apoptosis inductors [26, 27] have provided much needed motivation for continuous development of new (3-lactam systems. 

Another approach to a-ketoamide peptide mimetics was employed by Xu et al. [33] for the preparation of a human cytomegalovirus protease inhibitor library. In this case the oxidizable -OH group, protected as formate, belonged to the starting isocyanides. Thus, the reaction between N-acylated a-amino acids, amines, aldehydes, and isocyanides 42 afforded the a-hydroxyamides 43 in modest yields. Cleavage of the O-formyl bond was accomplished during the reaction by employing two... 

In 2002, Banfi and co-workers [39] further exploited this transformation to synthesize complex peptidomimetics exemplified by 29, a potent inhibitor of the serine proteases prolyl endo-peptidase [40] and Cytomegalovirus protease [41]. 

BP Holskin, M Bukhtiyarova, BM Dunn, P Baur, J de Chastonay, MW Pennington. A continuous fluorescence-based assay of human cytomegalovirus protease using a peptide substrate. Anal Biochem 226 148-155, 1995. 

Because of such extensive application in folk medicine, it is easy to understand the interest that the lapachol, the related naphthoquinones a-lapachone, P-lapachone and other naphthoquinones derivatives, have aroused as potential drugs. In fact, a broad variety of biological activities have been described for this kind of compounds. Some examples are antitumor promoting activities [11-12], inactivators of human cytomegalovirus protease [13], antiprotozoal activity [14], trypanocidal activity [15], anticancer activity [16], and antibacterial and antifungal activities [17]. 

Tong, L., Qian, C., Massariol, M. J., Deziel, R., Yoakim, C., and Lagace, L. (1998). Conserved mode of peptidomimetic inhibition and substrate recognition of human cytomegalovirus protease. Nat. Struct. Biol. 5, 819-826. 

Baum, E. Z Johnston, S. H., Bebemitz, G. A., and Gluzman, Y. (1996) Development of a scintillation proximity assay for human cytomegalovirus protease using 33Phosphorous. Anal. Biochem. 237,129-134. 

---