1.Cost-effectiveness of boceprevir in patients previously treated for chronic hepatitis C genotype 1 infection in the United States.
Chhatwal J1, Ferrante SA, Brass C, El Khoury AC, Burroughs M, Bacon B, Esteban-Mur R, Elbasha EH. Value Health. 2013 Sep-Oct;16(6):973-86. doi: 10.1016/j.jval.2013.07.006.
OBJECTIVES: The phase 3 trial, Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol-2 (RESPOND-2), demonstrated that the addition of boceprevir (BOC) to peginterferon-ribavirin (PR) resulted in significantly higher rates of sustained virologic response (SVR) in previously treated patients with chronic hepatitis C virus (HCV) genotype-1 infection as compared with PR alone. We evaluated the cost-effectiveness of treatment with BOC in previously treated patients with chronic hepatitis C in the United States using treatment-related data from RESPOND-2 and PROVIDE studies.
2.Baseline prevalence and emergence of protease inhibitor resistance mutations following treatment in chronic HCV genotype-1-infected individuals.
Nguyen LT1, Gray E, Dean J, Carr M, Connell J, De Gascun C, Nguyen LA, O'Leary A, Bergin C, Hall W, Norris S. Antivir Ther. 2015;20(8):865-9. doi: 10.3851/IMP2964. Epub 2015 Apr 29.
BACKGROUND: The HCV NS3/4A serine protease inhibitors (PIs) boceprevir (BOC), telaprevir (TVR) and simeprevir (SMV) are approved for treatment of chronic hepatitis C infection in combination with pegylated interferon and ribavirin. The present study investigated the prevalence of HCV NS3 drug resistance mutations (DRMs) associated with HCV genotype-1-infected individuals at baseline and in viral breakthrough following BOC and TVR treatment.
3.Pentapeptide boronic acid inhibitors of Mycobacterium tuberculosis MycP1 protease.
Frasinyuk MS1, Kwiatkowski S2, Wagner JM3, Evans TJ3, Reed RW3, Korotkov KV3, Watt DS4. Bioorg Med Chem Lett. 2014 Aug 1;24(15):3546-8. doi: 10.1016/j.bmcl.2014.05.056. Epub 2014 May 27.
Mycosin protease-1 (MycP1) cleaves ESX secretion-associated protein B (EspB) that is a virulence factor of Mycobacterium tuberculosis, and accommodates an octapeptide, AVKAASLG, as a short peptide substrate. Because peptidoboronic acids are known inhibitors of serine proteases, the synthesis and binding of a boronic acid analog of the pentapeptide cleavage product, AVKAA, was studied using MycP1 variants from Mycobacterium thermoresistible (MycP1mth), Mycobacterium smegmatis (MycP1msm) and M. tuberculosis (MycP1mtu). We synthesized the boropentapeptide, HAlaValLysAlaAlaB(OH)2 (1) and the analogous pinanediol PD-protected HAlaValLysAlaAlaBO2(PD) (2) using an Fmoc/Boc peptide strategy. The pinanediol boropentapeptide 2 displayed IC50 values 121.6±25.3 μM for MycP1mth, 93.2±37.3 μM for MycP1msm and 37.9±5.2 μM for MycP1mtu. Such relatively strong binding creates a chance for crystalizing the complex with 2 and finding the structure of the unknown MycP1 catalytic site that would potentially facilitate the development of new anti-tuberculosis drugs.
4.Efficient asymmetric synthesis of N-protected-β-aryloxyamino acids via regioselective ring opening of serine sulfamidate carboxylic acid.
Malhotra R1, Dey TK, Dutta S, Basu S, Hajra S. Org Biomol Chem. 2014 Sep 7;12(33):6507-15. doi: 10.1039/c4ob01047g.
First regioselective ring opening of serine derived cyclic sulfamidate by hard nucleophiles like ArONa is developed, where β-elimination of serine sulfamidate ester by stronger nucleophiles is overcome by reversal of the electronic effect of the carboxylate anion. This method provides easy and direct access to a variety of N-Boc- and N-PMB protected β-aryloxy-α-amino acids with complete retention of enantiopurity in moderate to high yields.
