01695nas a2200205   4500008004100000022001400041245012800055210006900183260010600252300001400358490000700372520082700379653002701206653003701233653001601270653003101286100002001317700002601337856012601363       2013                        eng d  a0968-089600aC-3 `-endo-puckered pyrrolidine containing PNA has favorable geometry for RNA binding: novel ethano locked PNA (ethano-PNA)0 aC3 endopuckered pyrrolidine containing PNA has favorable geometr  aTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLANDbPERGAMON-ELSEVIER SCIENCE LTDcJUL  a4092-41010 v213 a<p>A novel peptide nucleic acid (PNA) analogue is designed with a constraint in the aminoethyl segment of the aegPNA backbone so that the dihedral angle beta is restricted within 60-80 degrees, compatible to form PNA:RNA duplexes. The designed monomer is further functionalized with positively charged amino-/guanidino-groups. The appropriately protected monomers were synthesized and incorporated into aegPNA oligomers at predetermined positions and their binding abilities with cDNA and RNA were investigated. A single incorporation of the modified PNA monomer into a 12-mer PNA sequence resulted in stronger binding with complementary RNA over cDNA. No significant changes in the CD signatures of the derived duplexes of modified PNA with complementary RNA were observed. (C) 2013 Elsevier Ltd. All rights reserved.</p>10aAntisense therapeutics10aConformationally constrained PNA10aDiagnostics10aPeptide nucleic acid (PNA)1 aBanerjee, Anjan1 aKumar, Vaijayanti, A.  uhttp://library.ncl.res.in/content/c-3-endo-puckered-pyrrolidine-containing-pna-has-favorable-geometry-rna-binding-novel-002544nas a2200277   4500008004100000022001400041245012300055210006900178260000800247300001100255490000800266520161900274653001301893653002601906653001401932653001601946653001901962653001701981653003101998100002102029700002702050700002202077700002402099700001802123856012502141       2021                        eng d  a0882-401000aPNA-mediated efflux inhibition as a therapeutic strategy towards overcoming drug resistance in Mycobacterium smegmatis0 aPNAmediated efflux inhibition as a therapeutic strategy towards   cFEB  a1047370 v1513 a<p>The emergence of antibiotic-resistant strains of Mycobacterium tuberculosis and the decelerating development of new and effective antibiotics has impaired the treatment of tuberculosis (TB). Efflux pump inhibitors (EPIs) have the potential to improve the efficacy of existing anti-TB drugs although with toxicity limitations. Peptide nucleic acids (PNAs), oligonucleotide mimics, by virtue of their high nucleic acid binding specificity have the capability to overcome this drawback. We, therefore, investigated the efflux pump inhibitory properties of a PNA designed against an efflux pump of Mycobacterium smegmatis. LfrA, an efflux pump found in M. smegmatis, is majorly involved in conferring innate drug resistance to this strain and, therefore, was selected as a target for gene silencing via PNA. qRT-PCR and EtBr assays confirmed the EPI activity of the anti-lfrA PNA. On testing the effect of the anti-lfrA PNA on the bactericidal activity of a fluoroquinolone, norfloxacin, we observed that 5 mu M of anti-lfrA PNA in combination with norfloxacin led to an enhanced killing of up to 2.5 log-fold against wild-type and a lab-generated multidrug resistant strain, exemplifying its potential in countering resistance. Improved efficacy was also observed against intra-macrophage mycobacteria, where the drug-PNA combination enhanced bacterial clearance by 1.3 log-fold. Further, no toxicity was observed with PNA concentrations up to 4 times higher than the efficacious anti-lfrA PNA concentration. Thus, PNA, as an adjuvant, presents a novel and viable approach to rejuvenate anti-TB therapeutics.</p>
10aAdjuvant10aAntibiotic resistance10aAntisense10aEfflux pump10aGene silencing10aMycobacteria10aPeptide nucleic acid (PNA)1 aGhosh, Saptarshi1 aCotta, Karishma, Berta1 aHande, Aniket, A.1 aFernandes, Moneesha1 aMehra, Sarika  uhttp://library.ncl.res.in/content/pna-mediated-efflux-inhibition-therapeutic-strategy-towards-overcoming-drug-resistance