https://libjncir.jncasr.ac.in/xmlui/handle/10572/1531 2026-04-04T05:31:58Z 2026-04-04T05:31:58Z Rajasekhar, Kolla Narayanaswamy, Nagarjun Mishra, Piyush Suresh, S. N. Manjithaya, Ravi Govindaraju, T. https://libjncir.jncasr.ac.in/xmlui/handle/10572/2489 2017-02-21T10:24:33Z 2014-01-01T00:00:00Z

Synthesis of Hybrid Cyclic Peptoids and Identification of Autophagy Enhancer Rajasekhar, Kolla; Narayanaswamy, Nagarjun; Mishra, Piyush; Suresh, S. N.; Manjithaya, Ravi; Govindaraju, T. Cyclic peptoids are potential candidates for diverse biological activities. However, applications of cyclic peptoids are limited by the synthetic difficulties, conformational flexibility of large cyclic peptoids, and lack of secondary amide in the backbone. Herein, an elegant methodology for the synthesis of small and medium-size cyclic hybrid peptoids is developed. N-alpha-Alkyl and N-alpha-acyl substituents in N-(2-aminoethyl) glycine monomers enforce intra-and intermolecular cyclization to form stable six-and 12-membered cyclic products, respectively. NMR studies show inter-and intramolecular hydrogen bonding in six-and 12-membered cyclic peptoids, respectively. Screening of a cyclic peptoid library resulted in the identification of a potential candidate that enhanced autophagic degradation of cargo in a live cell model. Such upregulation of autophagy using small molecules is a promising approach for elimination of intracellular pathogens and neurodegenerative protein aggregates. Restricted Access

2014-01-01T00:00:00Z Kashi, Venkatesh P. Jacob, Rajesh A. Shamanna, Raghavendra A. Menon, Malini Balasiddaiah, Anangi Varghese, Rebu K. Bachu, Mahesh Ranga, Udaykumar https://libjncir.jncasr.ac.in/xmlui/handle/10572/2482 2017-02-21T10:24:38Z 2014-01-01T00:00:00Z

The Grafting of Universal T-Helper Epitopes Enhances Immunogenicity of HIV-1 Tat Concurrently Improving Its Safety Profile Kashi, Venkatesh P.; Jacob, Rajesh A.; Shamanna, Raghavendra A.; Menon, Malini; Balasiddaiah, Anangi; Varghese, Rebu K.; Bachu, Mahesh; Ranga, Udaykumar Extracellular Tat (eTat) plays an important role in HIV-1 pathogenesis. The presence of anti-Tat antibodies is negatively correlated with disease progression, hence making Tat a potential vaccine candidate. The cytotoxicity and moderate immunogenicity of Tat however remain impediments for developing Tat-based vaccines. Here, we report a novel strategy to concurrently enhance the immunogenicity and safety profile of Tat. The grafting of universal helper T-lymphocyte (HTL) epitopes, Pan DR Epitope (PADRE) and Pol(711) into the cysteine rich domain (CRD) and the basic domain (BD) abolished the transactivation potential of the Tat protein. The HTL-Tat proteins elicited a significantly higher titer of antibodies as compared to the wild-type Tat in BALB/c mice. While the N-terminal epitope remained immunodominant in HTL-Tat immunizations, an additional epitope in exon-2 was recognized with comparable magnitude suggesting a broader immune recognition. Additionally, the HTL-Tat proteins induced cross-reactive antibodies of high avidity that efficiently neutralized exogenous Tat, thus blocking the activation of a Tat-defective provirus. With advantages such as presentation of multiple B-cell epitopes, enhanced antibody response and importantly, transactivation-deficient Tat protein, this approach has potential application for the generation of Tat-based HIV/AIDS vaccines. Open Access

2014-01-01T00:00:00Z Jose, Diego Pandelo Bartholomeeusen, Koen da Cunha, Rodrigo Delvecchio Abreu, Celina Monteiro Glinski, Jan Ferreira da Costa, Thais Barbizan Mello Bacchi Rabay, Ana Flavia Pianowski Filho, Luiz Francisco Dudycz, Lech W. Ranga, Udaykumar Peterlin, Boris Matija Pianowski, Luiz Francisco Tanuri, Amilcar Aguiar, Renato Santana https://libjncir.jncasr.ac.in/xmlui/handle/10572/2481 2017-02-21T10:24:29Z 2014-01-01T00:00:00Z

Reactivation of latent HIV-1 by new semi-synthetic ingenol esters Jose, Diego Pandelo; Bartholomeeusen, Koen; da Cunha, Rodrigo Delvecchio; Abreu, Celina Monteiro; Glinski, Jan; Ferreira da Costa, Thais Barbizan; Mello Bacchi Rabay, Ana Flavia; Pianowski Filho, Luiz Francisco; Dudycz, Lech W.; Ranga, Udaykumar; Peterlin, Boris Matija; Pianowski, Luiz Francisco; Tanuri, Amilcar; Aguiar, Renato Santana The ability of HIV to establish long-lived latent infection is mainly due to transcriptional silencing of viral genome in resting memory T lymphocytes. Here, we show that new semi-synthetic ingenol esters reactivate latent HIV reservoirs. Amongst the tested compounds, 3-caproyl-ingenol (ING B) was more potent in reactivating latent HIV than known activators such as SAHA, ingenol 3,20-dibenzoate, TNF-alpha, PMA and HMBA. ING B activated PKC isoforms followed by NF-kappa B nuclear translocation. As virus reactivation is dependent on intact NF-kappa B binding sites in the LTR promoter region ING B, we have shown that. ING B was able to reactivate virus transcription in primary HIV-infected resting cells up to 12 fold and up to 25 fold in combination with SAHA. Additionally, ING B promoted up-regulation of P-TEFb subunits CDK9/Cyclin TI. The role of ING B on promoting both transcription initiation and elongation makes this compound a strong candidate for an anti-HIV latency drug combined with suppressive HAART. (C) 2014 Elsevier Inc. All rights reserved. Restricted Access

2014-01-01T00:00:00Z Ramana, Lakshmi Narashimhan Sharma, Shilpee Sethuraman, Swaminathan Ranga, Udaykumar Krishnan, Uma Maheswari https://libjncir.jncasr.ac.in/xmlui/handle/10572/2479 2017-02-21T10:24:35Z 2014-01-01T00:00:00Z

Evaluation of chitosan nanoformulations as potent anti-HIV therapeutic systems Ramana, Lakshmi Narashimhan; Sharma, Shilpee; Sethuraman, Swaminathan; Ranga, Udaykumar; Krishnan, Uma Maheswari Background: Antiretroviral Therapy (ART) is currently the major therapeutic intervention in the treatment of AIDS. ART, however, is severely limited due to poor availability, high cytotoxicity, and enhanced metabolism and clearance of the drug molecules by the renal system. The use of nanocarriers encapsulating the antiretroviral drugs may provide a solution to the aforementioned problems. Importantly, the application of mildly immunogenic polymeric carrier confers the advantage of making the nanoparticles more visible to the immune system leading to their efficient uptake by the phagocytes. Methods: The saquinavir-loaded chitosan nanopartides were characterized by transmission electron microscopy and differential scanning calorimetry and analyzed for the encapsulation efficiency, swelling characteristics, particle size properties, and the zeta potential. Furthermore, cellular uptake of the chitosan nanocarriers was evaluated using confocal microscopy and Flow cytometry. The antiviral efficacy was quantified using viral infection of the target cells. Results: Using novel chitosan carriers loaded with saquinavir, a protease inhibitor, we demonstrate a drug encapsulation efficiency of 75% and cell targeting efficiency greater than 92%. As compared to the soluble drug control, the saquinavir-loaded chitosan carriers caused superior control of the viral proliferation as measured by using two different viral strains, NL4-3 and Indie-C1, and two different target T-cells, Jurkat and CEM-CCR5. Conclusion: Chitosan nanoparticles loaded with saquinavir were characterized and they demonstrated superior drug loading potential with greater cell targeting efficiency leading to efficient control of the viral proliferation in target T-cells. General significance: Our data ascertain the potential of chitosan nanocarriers as novel vehicles for HIV-1 therapeutics. (C) 2013 Elsevier B.V. All rights reserved. Restricted Access

2014-01-01T00:00:00Z