Manufacturing of insulin and its analogues relied upon in vitro enzymatic cleavages of its precursor forms (single chain precursor, SCP) at both ends of a connecting peptide (C-peptide) that links the respective B-chain and A-chains to corresponding final forms. We have demonstrated a simplified approach of cleaving P. pastoris expressed SCP, distinctly at one site for conversion to insulin glargine.
View Article and Find Full Text PDFBackground: Fluoroquinolones (FQs) are being used as second-line agents in the treatment of tuberculosis caused by multidrug-resistant strains. Ofloxacin (OFX) is being tried as a part of modified multidrug therapy regimens for leprosy. A preliminary study was carried out to evaluate the accumulation of FQs - OFX, levofloxacin (LFX), norfloxacin (NFX), and ciprofloxacin (CIF) in Mycobacterium smegmatis.
View Article and Find Full Text PDFTuberculosis is an airborne infectious disease caused by Mycobacterium tuberculosis which threatens the globe. Aminoglycosides {Amikacin (AK) & Kanamycin (KM)} are WHO recommended second-line anti-TB drugs used against the treatment of drug-resistant tuberculosis. Aminoglycosides target the steps of protein translation machinery of M.
View Article and Find Full Text PDFEmergence of extensively drug resistant tuberculosis (XDR-TB) is the consequence of the failure of second line TB treatment. Aminoglycosides are the important second line anti-TB drugs used to treat the multi drug resistant tuberculosis (MDR-TB). Main known mechanism of action of aminoglycosides is to inhibit the protein synthesis by inhibiting the normal functioning of ribosome.
View Article and Find Full Text PDFTuberculosis is an infectious disease, caused by one of the most successful human pathogen, Mycobacterium tuberculosis. Aminoglycosides, Amikacin (AK) & Kanamycin (KM) are commonly used to treat drug resistant tuberculosis. They target the protein synthesis machinery by interacting with several steps of translation.
View Article and Find Full Text PDFAminoglycosides, amikacin (AK) and kanamycin (KM) are second line anti-tuberculosis drugs used to treat tuberculosis (TB) and resistance to them affects the treatment. Membrane and membrane associated proteins have an anticipated role in biological processes and pathogenesis and are potential targets for the development of new diagnostics/vaccine/therapeutics. In this study we compared membrane and membrane associated proteins of AK and KM resistant and susceptible Mycobacterium tuberculosis isolates by 2DE coupled with MALDI-TOF/TOF-MS and bioinformatic tools.
View Article and Find Full Text PDFDrug resistance particularly, multi drug resistance tuberculosis (MDR-TB) has emerged as a major problem in the chemotherapy of tuberculosis. Ofloxacin (OFX) has been used as second-line drug against MDR-TB. The principal target of the OFX is DNA gyrase encoded by gyrA and gyrB genes.
View Article and Find Full Text PDFOfloxacin (OFX) and moxifloxacin (MOX) are the most promising second line drugs for tuberculosis treatment. Although the primary mechanism of action of OFX and MOX is gyrase inhibition, other possible mechanisms cannot be ruled out. Being the functional moiety of cell, the proteins act as primary targets for developing drugs, diagnostics and therapeutics.
View Article and Find Full Text PDFUnlabelled: Kanamycin (KM) and amikacin (AK) are the key aminoglycoside drugs against tuberculosis (TB) and resistance to them severely affects the options for treatment. Many explanations have been proposed for drug resistance to these drugs but still some mechanisms are unknown. Proteins are the functional moiety of the cell and manifest in most of the biological processes; so, these are potential foci for the development of new therapeutics, diagnostics and vaccine.
View Article and Find Full Text PDFProtein mannosyltransferases (PMTs) catalyze the O-mannosylation of serine and threonine residues of proteins in the endoplasmic reticulum. The five PMT genes coding for protein mannosyltransferases, designated as PMT1, 2, 4, 5 and 6, were identified from Pichia pastoris genome based on the homology to PMT genes in Saccharomyces cerevisiae genome, which has seven PMT genes. The homologues of S.
View Article and Find Full Text PDFBackground: Streptomycin (SM) is a broad spectrum antibiotic and is an important component of any anti-tuberculosis therapy regimen. Several mechanisms have been proposed to explain the emergence of resistance but still our knowledge is inadequate. Proteins form a very complex network and drugs are countered by their modification/efflux or over expression/modification of targets.
View Article and Find Full Text PDFBackground & Objectives: The resistance of Mycobacterium tuberculosis to streptomycin, a core drug for treatment of category II tuberculosis (TB) has posed a major challenge to the health providers as well as research workers worldwide and has severely compromised the therapeutic options. A significant proportion of streptomycin resistant M. tuberculosis isolates failed to show mutations in conventional targets like rpsL and rrs.
View Article and Find Full Text PDFTreatment of multidrug-resistant tuberculosis has become one of the major problems in public health. Understanding the molecular mechanisms of drug resistance has been central to tuberculosis research in recent times. DNA microarray technology provides the platform to study the genomic variations related to these mechanisms on a comprehensive level.
View Article and Find Full Text PDFTissue distribution and deposition of clofazimine (CAS 2030-63-9) in mice were investigated following administration of clofazimine with or without isoniazid (CAS 54-85-3). Balb/c mice were administered clofazimine suspension in mustard oil orally at a daily dose of 20 mg/kg body weight either alone or along with isoniazid (10 mg/kg body weight) for 15 or 30 days. Various tissues (liver, lung, spleen, small intestine, heart, kidneys, mesentric fat, foot pad and nerve) and pooled plasma were analysed for clofazimine in all the treated groups.
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