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  1. AU=Jagadish Krishnappa
  2. AU="Reina, Miguel A"
  3. AU="Lim, Huey-Yee"
  4. AU="Carla M. Carvalho"
  5. AU="Aghaei Zarch, Seyed Mohsen"
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  10. AU="Jin Han Nam"
  11. AU="Millburn, Michael V"
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  13. AU="Granich, R"
  14. AU="Koh, Lian Chye Winston"
  15. AU="Meredith M. White"
  16. AU="Aft, Rebecca"
  17. AU="Urban, Gerald A"
  18. AU="Jeong, Jae-Hyun"
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  1. Artikel ; Online: Recombinant Expression of Cyclotides Using Split Inteins.

    Jagadish, Krishnappa / Camarero, Julio A

    Methods in molecular biology (Clifton, N.J.)

    2017  Band 1495, Seite(n) 41–55

    Abstract: Cyclotides are fascinating microproteins (≈30 residues long) present in several families of plants that share a unique head-to-tail circular knotted topology of three disulfide bridges, with one disulfide penetrating through a macrocycle formed by the ... ...

    Abstract Cyclotides are fascinating microproteins (≈30 residues long) present in several families of plants that share a unique head-to-tail circular knotted topology of three disulfide bridges, with one disulfide penetrating through a macrocycle formed by the two other disulfides and inter-connecting peptide backbones, forming what is called a cystine knot topology. Naturally occurring cyclotides have shown to posses various pharmacologically relevant activities and have been reported to cross cell membranes. Altogether, these features make the cyclotide scaffold an excellent molecular framework for the design of novel peptide-based therapeutics, making them ideal substrates for molecular grafting of biological peptide epitopes. In this chapter we describe how to express a native folded cyclotide using intein-mediated protein trans-splicing in live Escherichia coli cells.
    Sprache Englisch
    Erscheinungsdatum 2017
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-6451-2_4
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel: Cyclotides, a promising molecular scaffold for peptide-based therapeutics.

    Jagadish, Krishnappa / Camarero, Julio A

    Biopolymers

    2010  Band 94, Heft 5, Seite(n) 611–616

    Abstract: Cyclotides are a new emerging family of large plant-derived backbone-cyclized polypeptides (approximately 30 amino acids long) that share a disulfide-stabilized core (three disulfide bonds) characterized by an unusual knotted structure. Their unique ... ...

    Abstract Cyclotides are a new emerging family of large plant-derived backbone-cyclized polypeptides (approximately 30 amino acids long) that share a disulfide-stabilized core (three disulfide bonds) characterized by an unusual knotted structure. Their unique circular backbone topology and knotted arrangement of three disulfide bonds make them exceptionally stable to thermal, chemical, and enzymatic degradation compared to other peptides of similar size. Currently, more than 100 sequences of different cyclotides have been characterized, and the number is expected to increase dramatically in the coming years. Considering their stability and biological activities like anti-HIV, uterotonic, and insecticidal, and also their abilities to cross the cell membrane, cyclotides can be exploited to develop new stable peptide-based drugs. We have recently demonstrated the intriguing possibility of producing libraries of cyclotides inside living bacterial cells. This opens the possibility to generate large genetically encoded libraries of cyclotides that can then be screened inside the cell for selecting particular biological activities in a high-throughput fashion. The present minireview reports the efforts carried out toward the selection of cyclotide-based compounds with specific biological activities for drug design.
    Mesh-Begriff(e) Amino Acid Sequence ; Cyclotides/biosynthesis ; Cyclotides/chemistry ; Cyclotides/genetics ; Cyclotides/therapeutic use ; Drug Design ; Models, Molecular ; Molecular Sequence Data ; Peptide Library ; Plant Proteins/biosynthesis ; Plant Proteins/chemistry ; Plant Proteins/genetics ; Plant Proteins/therapeutic use ; Protein Engineering ; Protein Structure, Tertiary ; Sequence Alignment ; Trypsin/chemistry
    Chemische Substanzen Cyclotides ; Peptide Library ; Plant Proteins ; Trypsin (EC 3.4.21.4)
    Sprache Englisch
    Erscheinungsdatum 2010-06-15
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1123-x
    ISSN 1097-0282 ; 0006-3525
    ISSN (online) 1097-0282
    ISSN 0006-3525
    DOI 10.1002/bip.21433
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Backbone dynamics of cyclotide MCoTI-I free and complexed with trypsin.

    Puttamadappa, Shadakshara S / Jagadish, Krishnappa / Shekhtman, Alexander / Camarero, Julio A

    Angewandte Chemie (International ed. in English)

    2010  Band 49, Heft 39, Seite(n) 7030–7034

    Mesh-Begriff(e) Amino Acid Sequence ; Cyclotides/chemistry ; Cyclotides/genetics ; Cyclotides/metabolism ; Magnetic Resonance Spectroscopy ; Molecular Sequence Data ; Plant Proteins/chemistry ; Plant Proteins/genetics ; Plant Proteins/metabolism ; Protein Binding ; Protein Structure, Tertiary ; Recombinant Proteins/chemistry ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; Trypsin/chemistry ; Trypsin/metabolism ; Trypsin Inhibitors/chemistry
    Chemische Substanzen Cyclotides ; MCoTI-I protein, Momordica cochinchinensis ; Plant Proteins ; Recombinant Proteins ; Trypsin Inhibitors ; Trypsin (EC 3.4.21.4)
    Sprache Englisch
    Erscheinungsdatum 2010-10-08
    Erscheinungsland Germany
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2011836-3
    ISSN 1521-3773 ; 1433-7851
    ISSN (online) 1521-3773
    ISSN 1433-7851
    DOI 10.1002/anie.201002906
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Expression of fluorescent cyclotides using protein trans-splicing for easy monitoring of cyclotide-protein interactions.

    Jagadish, Krishnappa / Borra, Radhika / Lacey, Vanessa / Majumder, Subhabrata / Shekhtman, Alexander / Wang, Lei / Camarero, Julio A

    Angewandte Chemie (International ed. in English)

    2013  Band 52, Heft 11, Seite(n) 3126–3131

    Mesh-Begriff(e) Amino Acid Sequence ; Click Chemistry ; Cyclotides/biosynthesis ; Cyclotides/chemistry ; Cyclotides/genetics ; Cyclotides/metabolism ; Fluorescence ; Models, Molecular ; Molecular Sequence Data ; Protein Engineering ; Trans-Splicing
    Chemische Substanzen Cyclotides
    Sprache Englisch
    Erscheinungsdatum 2013-01-15
    Erscheinungsland Germany
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2011836-3
    ISSN 1521-3773 ; 1433-7851
    ISSN (online) 1521-3773
    ISSN 1433-7851
    DOI 10.1002/anie.201209219
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Recombinant Expression and Phenotypic Screening of a Bioactive Cyclotide Against α-Synuclein-Induced Cytotoxicity in Baker's Yeast.

    Jagadish, Krishnappa / Gould, Andrew / Borra, Radhika / Majumder, Subhabrata / Mushtaq, Zahid / Shekhtman, Alexander / Camarero, Julio A

    Angewandte Chemie (International ed. in English)

    2015  Band 54, Heft 29, Seite(n) 8390–8394

    Abstract: We report for the first time the recombinant expression of fully folded bioactive cyclotides inside live yeast cells by using intracellular protein trans-splicing in combination with a highly efficient split-intein. This approach was successfully used to ...

    Abstract We report for the first time the recombinant expression of fully folded bioactive cyclotides inside live yeast cells by using intracellular protein trans-splicing in combination with a highly efficient split-intein. This approach was successfully used to produce the naturally occurring cyclotide MCoTI-I and the engineered bioactive cyclotide MCoCP4. Cyclotide MCoCP4 was shown to reduce the toxicity of human α-synuclein in live yeast cells. Cyclotide MCoCP4 was selected by phenotypic screening from cells transformed with a mixture of plasmids encoding MCoCP4 and inactive cyclotide MCoTI-I in a ratio of 1:5×10(4). This demonstrates the potential for using yeast to perform phenotypic screening of genetically encoded cyclotide-based libraries in eukaryotic cells.
    Mesh-Begriff(e) Amino Acid Sequence ; Cyclotides/chemistry ; Cyclotides/genetics ; Cyclotides/pharmacology ; Humans ; Models, Molecular ; Molecular Sequence Data ; Protein Engineering ; Recombinant Proteins/chemistry ; Recombinant Proteins/genetics ; Recombinant Proteins/pharmacology ; Saccharomyces cerevisiae/cytology ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Trans-Splicing ; Transformation, Genetic ; alpha-Synuclein/metabolism
    Chemische Substanzen Cyclotides ; Recombinant Proteins ; SNCA protein, human ; alpha-Synuclein
    Sprache Englisch
    Erscheinungsdatum 2015-06-10
    Erscheinungsland Germany
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2011836-3
    ISSN 1521-3773 ; 1433-7851
    ISSN (online) 1521-3773
    ISSN 1433-7851
    DOI 10.1002/anie.201501186
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel: Backbone Dynamics of Cyclotide MCoTI-I Free and Complexed with Trypsin

    Puttamadappa, Shadakshara S / Jagadish, Krishnappa / Shekhtman, Alexander / Camarero, Julio A

    Angewandte Chemie. 2010 Sept. 17, v. 49, no. 39

    2010  

    Sprache Englisch
    Erscheinungsverlauf 2010-0917
    Umfang p. 7030-7034.
    Erscheinungsort Wiley-VCH Verlag
    Dokumenttyp Artikel
    ZDB-ID 2011836-3
    ISSN 1521-3773 ; 1433-7851
    ISSN (online) 1521-3773
    ISSN 1433-7851
    DOI 10.1002/anie.201002906
    Datenquelle NAL Katalog (AGRICOLA)

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  7. Artikel ; Online: Hypothermia for moderate or severe neonatal encephalopathy in low-income and middle-income countries (HELIX): a randomised controlled trial in India, Sri Lanka, and Bangladesh.

    Thayyil, Sudhin / Pant, Stuti / Montaldo, Paolo / Shukla, Deepika / Oliveira, Vania / Ivain, Phoebe / Bassett, Paul / Swamy, Ravi / Mendoza, Josephine / Moreno-Morales, Maria / Lally, Peter J / Benakappa, Naveen / Bandiya, Prathik / Shivarudhrappa, Indramma / Somanna, Jagadish / Kantharajanna, Usha B / Rajvanshi, Ankur / Krishnappa, Sowmya / Joby, Poovathumkal K /
    Jayaraman, Kumutha / Chandramohan, Rema / Kamalarathnam, Chinnathambi N / Sebastian, Monica / Tamilselvam, Indumathi A / Rajendran, Usha D / Soundrarajan, Radhakrishnan / Kumar, Vignesh / Sudarsanan, Harish / Vadakepat, Padmesh / Gopalan, Kavitha / Sundaram, Mangalabharathi / Seeralar, Arasar / Vinayagam, Prakash / Sajjid, Mohamed / Baburaj, Mythili / Murugan, Kanchana D / Sathyanathan, Babu P / Kumaran, Elumalai S / Mondkar, Jayashree / Manerkar, Swati / Joshi, Anagha R / Dewang, Kapil / Bhisikar, Swapnil M / Kalamdani, Pavan / Bichkar, Vrushali / Patra, Saikat / Jiwnani, Kapil / Shahidullah, Mohammod / Moni, Sadeka C / Jahan, Ismat / Mannan, Mohammad A / Dey, Sanjoy K / Nahar, Mst N / Islam, Mohammad N / Shabuj, Kamrul H / Rodrigo, Ranmali / Sumanasena, Samanmali / Abayabandara-Herath, Thilini / Chathurangika, Gayani K / Wanigasinghe, Jithangi / Sujatha, Radhika / Saraswathy, Sobhakumar / Rahul, Aswathy / Radha, Saritha J / Sarojam, Manoj K / Krishnan, Vaisakh / Nair, Mohandas K / Devadas, Sahana / Chandriah, Savitha / Venkateswaran, Harini / Burgod, Constance / Chandrasekaran, Manigandan / Atreja, Gaurav / Muraleedharan, Pallavi / Herberg, Jethro A / Kling Chong, W K / Sebire, Neil J / Pressler, Ronit / Ramji, Siddarth / Shankaran, Seetha

    The Lancet. Global health

    2021  Band 9, Heft 9, Seite(n) e1273–e1285

    Abstract: Background: Although therapeutic hypothermia reduces death or disability after neonatal encephalopathy in high-income countries, its safety and efficacy in low-income and middle-income countries is unclear. We aimed to examine whether therapeutic ... ...

    Abstract Background: Although therapeutic hypothermia reduces death or disability after neonatal encephalopathy in high-income countries, its safety and efficacy in low-income and middle-income countries is unclear. We aimed to examine whether therapeutic hypothermia alongside optimal supportive intensive care reduces death or moderate or severe disability after neonatal encephalopathy in south Asia.
    Methods: We did a multicountry open-label, randomised controlled trial in seven tertiary neonatal intensive care units in India, Sri Lanka, and Bangladesh. We enrolled infants born at or after 36 weeks of gestation with moderate or severe neonatal encephalopathy and a need for continued resuscitation at 5 min of age or an Apgar score of less than 6 at 5 min of age (for babies born in a hospital), or both, or an absence of crying by 5 min of age (for babies born at home). Using a web-based randomisation system, we allocated infants into a group receiving whole body hypothermia (33·5°C) for 72 h using a servo-controlled cooling device, or to usual care (control group), within 6 h of birth. All recruiting sites had facilities for invasive ventilation, cardiovascular support, and access to 3 Tesla MRI scanners and spectroscopy. Masking of the intervention was not possible, but those involved in the magnetic resonance biomarker analysis and neurodevelopmental outcome assessments were masked to the allocation. The primary outcome was a combined endpoint of death or moderate or severe disability at 18-22 months, assessed by the Bayley Scales of Infant and Toddler Development (third edition) and a detailed neurological examination. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02387385.
    Findings: We screened 2296 infants between Aug 15, 2015, and Feb 15, 2019, of whom 576 infants were eligible for inclusion. After exclusions, we recruited 408 eligible infants and we assigned 202 to the hypothermia group and 206 to the control group. Primary outcome data were available for 195 (97%) of the 202 infants in the hypothermia group and 199 (97%) of the 206 control group infants. 98 (50%) infants in the hypothermia group and 94 (47%) infants in the control group died or had a moderate or severe disability (risk ratio 1·06; 95% CI 0·87-1·30; p=0·55). 84 infants (42%) in the hypothermia group and 63 (31%; p=0·022) infants in the control group died, of whom 72 (36%) and 49 (24%; p=0·0087) died during neonatal hospitalisation. Five serious adverse events were reported: three in the hypothermia group (one hospital readmission relating to pneumonia, one septic arthritis, and one suspected venous thrombosis), and two in the control group (one related to desaturations during MRI and other because of endotracheal tube displacement during transport for MRI). No adverse events were considered causally related to the study intervention.
    Interpretation: Therapeutic hypothermia did not reduce the combined outcome of death or disability at 18 months after neonatal encephalopathy in low-income and middle-income countries, but significantly increased death alone. Therapeutic hypothermia should not be offered as treatment for neonatal encephalopathy in low-income and middle-income countries, even when tertiary neonatal intensive care facilities are available.
    Funding: National Institute for Health Research, Garfield Weston Foundation, and Bill & Melinda Gates Foundation.
    Translations: For the Hindi, Malayalam, Telugu, Kannada, Singhalese, Tamil, Marathi and Bangla translations of the abstract see Supplementary Materials section.
    Mesh-Begriff(e) Bangladesh/epidemiology ; Brain Diseases/mortality ; Brain Diseases/therapy ; Developing Countries ; Female ; Humans ; Hypothermia, Induced ; India/epidemiology ; Infant, Newborn ; Intensive Care, Neonatal ; Male ; Severity of Illness Index ; Sri Lanka/epidemiology ; Treatment Outcome
    Sprache Englisch
    Erscheinungsdatum 2021-08-03
    Erscheinungsland England
    Dokumenttyp Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 2723488-5
    ISSN 2214-109X ; 2214-109X
    ISSN (online) 2214-109X
    ISSN 2214-109X
    DOI 10.1016/S2214-109X(21)00264-3
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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