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Applicability of KEAP1 E3 Ligase to the PROTAC Platform
Raju Gurung(Raju Gurung),Jae Rim Lee(Jae Rim Lee),Min Ju Cho(Min Ju Cho),Jin Ah Jeong(Jin Ah Jeong),Sung Jean Park(Sung Jean Park),Kwang Won Jeong(Kwang Won Jeong),Dongyun Shin(Dongyun Shin) 대한약학회 2024 약학회지 Vol.68 No.4
Proteolysis-targeting chimeras (PROTACs) represent an innovative approach for drug design involving the creation of a heterobifunctional molecule. This molecule uses an E3 ligase to target and degrade specific proteins via the ubiquitin-proteasome system (UPS). The three essential components of PROTAC are a ligand for the protein of interest (POI), a binder to recruit an E3 ligase, and a linker connecting these two elements. Given the relatively large number of E3 ligases in the human body (>600), only a few such as VHL, CRBN, MDM2, cIAP1, DCAF15, RNF4, and RNF114 have been used in existing PROTACs. PROTACs facilitate degradation of pathological proteins through the UPS pathway. Consequently, the identification of a broad range of E3 ligase recruiters is crucial for advancing targeted protein degradation (TPD) strategies. In this study, we focused on designing KEAP1 binder PROTACs, using a selective, potent small-molecule inhibitor of KEAP1 as an E3 ligase recruiter. It was linked to JQ1 (a POI ligand) via a flexible aliphatic linker. Our compound SD-2406, with KEAP1 E3 ligase recruiter, effectively degraded BRD4 target proteins in LNCaP cells. This demonstrates the potential of expanding the E3 ligase toolbox for the development of PROTAC technology.
Analytical Models to Predict Power Harvesting with Piezoelectric Transducer
Raghava Raju Muppala,K. Padma Raju,Nam Mee Moon,Baek Ho Jung 한국전자파학회JEES 2008 Journal of Electromagnetic Engineering and Science Vol.8 No.1
Advances in low power design open the possibility to harvest energy from the environment to power electronic circuits. Electrical energy can be harvested from piezoelectric transducer. Piezoelectric materials can be used as mechanisms to transfer mechanical energy usually vibrating system into electrical energy that can be stored and used to power other devices. Micro- to milli-watts power can be generated from vibrating system. We developed definitive and analytical models to predict the power generated from a cantilever beam attached with piezoelectric transducer. Analytical models are pin-force method, enhanced pin-force method and Euler-Bernoulli method. Harmonic oscillations and random noise will be the two different forcing functions used to drive each system. It has been selected the best model for generating electric power based upon the analytical results obtained.
Sirangi, Subash,Jogam, Phanikanth,Nemali, Gandhi,Ajmeera, Ragan,Abbagani, Sadanandam,Raju, Vatsavaya S. The Korean Society of Plant Biotechnology 2020 JOURNAL OF PLANT BIOTECHNOLOGY Vol.47 No.4
The genetic diversity of two subpopulations of Corynandra chelidonii, one of terrestrial and the other of aquatic environments, was measured with molecular markers, such as start codon targeted (SCoT), inter simple sequence repeats (ISSR), and random amplification of polymorphic DNA (RAPD). The traditional morphological traits such as habitat, habit, leaf morphology, the colour of the sepals and petals, number of stamens, and seed morphology formed the base for their realization as two varieties, C. chelidonii var. pallae and C. chelidonii var. chelidonii. The polymorphism between the two variants was 100% with the primers SCoT-2 and OPA-1 and 4, while maximum polymorphism was detected with ISSR-2, SCoT-3, and OPA-3. The study used, for the first time, more than one molecular marker to assess the genetic variation underscoring the morphological variation in Corynandra chelidonii (L.f.) Cochrane & Iltis. The study justifies the recognition of the two subpopulations of Corynandra chelidonii from aquatic and terrestrial environments as two distinct varieties, C. chelidonii var. pallae (Reddy & Raju) V.S.Raju and C. chelidonii var. chelidonii, respectively, based on the traditional taxonomic evidence.
Raju, M.V.L.N.,Devegowda, G. Asian Australasian Association of Animal Productio 2002 Animal Bioscience Vol.15 No.7
In vitro binding efficacy of esterified glucomannan (E-GM) (0.1%) on aflatoxin B1 (AF) (300 ppb), ochratoxin A (OA) (2 ppm) and T-2 toxin (T-2) (3 ppm), when present alone or in combination, was evaluated in toxin-contaminated feed at pH 4.5 and 6.5. Esterified glucomannan showed significantly (p<0.01) higher binding with AF (81.6%), whereas those recorded with T-2 (27.8%) and OA (25.6%) were moderate. Binding of each toxin decreased as the number of toxins in feed increased. pH of medium showed no effect on mycotoxin binding ability of E-GM. A $2{\times}2{\times}2{\times}2$ factorial experiment of 5 week duration was conducted to study the effects of two dietary levels each of AF (0 and 300 ppb), OA (0 and 2 ppm), T-2 (0 and 3 ppm ) and E-GM (0 and 0.1%) on the immune competence of a total of 960 day-old commercial broilers. Reductions in size of thymus (by AF and T-2) and bursa (by AF) and antibody titers against Newcastle disease and Infectious Bursal disease (by all the toxins) were noted. Additive and antagonistic interactions were seen among the toxins on certain parameters. Esterified glucomannan significantly (p<0.01) improved antibody titers and weights of bursa ofFabricius and thymus indicating its counteracting efficacy against immunosuppression in mycotoxicosis of multiple origin.
Raju, G. Seeta Rama,Park, Jin Young,Jung, Hong Chae,Pavitra, E.,Moon, Byung Kee,Jeong, Jung Hyun,Kim, Jung Hwan Royal Society of Chemistry 2011 Journal of materials chemistry Vol.21 No.17
<P>The cathodoluminescence and the excitation induced photoluminescence properties have been investigated for the nanocrystalline Tb<SUP>3+</SUP>/Sm<SUP>3+</SUP>:Ca<SUB>2</SUB>Gd<SUB>8</SUB>Si<SUB>6</SUB>O<SUB>26</SUB> phosphors prepared by a solvothermal reaction method. The XRD patterns confirm their hexagonal structure. The green, orange and white emissions have been obtained by exciting at 275, 378, and 405 nm wavelengths, respectively. The corresponding CIE chromaticity coordinates are found to be in close proximity to the standard points in their respective regions. The cathodoluminescence at low accelerating voltage has also covered the entire visible region, resulting in white emission. These luminescent powders are expected to find potential applications in the development of LEDs and FEDs.</P> <P>Graphic Abstract</P><P>Single-emitting component (Tb<SUP>3+</SUP>/Sm<SUP>3+</SUP>:Ca<SUB>2</SUB>Gd<SUB>8</SUB>Si<SUB>6</SUB>O<SUB>26</SUB> phosphor) produces the white light as well as individual colors at different excitation wavelengths. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c0jm04337k'> </P>
Raju Madanala,Vijayta Gupta,Rakesh Tuli,Pradhyumna Kumar Singh 한국식물생명공학회 2012 Plant biotechnology reports Vol.6 No.1
Plastid transformation vectors are used for highlevel expression of industrially important recombinant proteins in plants. In the present study, new vectors for plastid transformation were developed. One of these vectors targets transgenes at a new site in the chloroplast genome. Intergenic regions of trnfM-trnG, ndhB-trnL and rrn16-trnV were selected as sites for transgene insertion. Tobacco chloroplast was successfully transformed with designed vectors, and the transplastomic plants accumulated recombinant protein as high as 5–6% of total soluble protein which remained localized in the chloroplasts. Although the vectors were designed using the plastid genome of Nicotiana tabacum, flanking regions used in two vectors show a high level of homology with chloroplast genomes of other plant species, thus it might be possible to use them for the transformation of a wider range of plant species.