90 research outputs found

    Design and synthesis of selective ligands for the FK506-binding protein 51

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    Design and synthesis of selective ligands for the FK506-binding protein 51

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    Phylogenic analysis in Acacia senegal using AFLP molecular markers across the Gum Arabic Belt in Sudan

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    Amplified fragment length polymorphism (AFLP) DNA markers were used to characterize the genetic diversity and relationships in gum Arabic tree (Acacia senegal). Twenty eight samples of Acacia senegal collected from populations distributed throughout the Gum Arabic belt were tested in comparison with samples of Acacia mellifera and Acacia leata. Nine AFLP selective primer pair combinations generated a total of 433 amplification products with an average of 89.18% detected polymorphisms. Accessions showed the least variation was found within the A. senegal accessions in contrast with mellifera and Acacia leata that presented the highest degree of polymorphism number. According to the cluster analysis two main clusters were obtained in which A. mellifera and A. leata were placed in a separate group. There were eight subgroups of A. Senegal. Three of the eight subgroups of A. senegal were clustered according to geographical origin. The variation within population might be correlated with abiotic factors of the environment

    Genetic variability in Sudanese Acacia senegal (L.) assessed by random amplified polymorphic DNA

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    Random Amplified polymorphic DNA (RAPD) markers were used to characterize the genetic diversity and relationships among (Acacia senegal). A total of 15 primers were tested with the 30 genotypes ofAcacia spp. (28 A. senegal, one A. mellifera and one A. leata). The results indicated that 7 primers (60%) showed at least 1 consistent polymorphic band. The seven informative primers were selected and used to evaluate the degree of polymorphism and genetic relationships within and among all the Acacia spp under study. The selected primers generated distinctive products in the range of 1.584-5.148 Kbp. Total of 51 amplified fragments were distinguished across the selected primers and the statistical analysisshowed 44 polymorphic bands among the 28 genotypes with an average of 7.2 polymorphic bands per primer. The maximum numbers of fragment bands were produced by the primer OPA-09 (11) with 73% polymorphism while the minimum numbers of fragments were produced by the primer OPA-01 (5) with 80% polymorphism Molecular variance (STATISTCA) was used to investigate the genetic diversity among individual. High level of polymorphism among individuals suggested that RAPD technique canbe useful for A. senegal for the maintenance of germplasm banks and the efficient selection of parents for breeding

    Genetic characterization of two Sudanese goat breeds (Capra hircus) using RAPD molecular markers

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    Seven primers of randomly amplified polymorphic DNA (RAPD) were selected to study the genetic variations among 14 individuals of goat (Capra hircus) from two domestic Sudanese goat breeds (Niloticand Nubian). The test generated 59 entirely repeatable RAPD fragment bands and the statistical analysis showed 55 polymorphic bands among the 14 individuals. The genetic distances among the populationrange from 8 to 72%. The highest dissimilarity coefficient was between individuals within the Nilotic breeds while there was a comparatively low degree of differentiation among the Nubian population. The constructed UPGMA dendrogram of the coefficient of similarity showed that the Nubian clustered together while the individuals from the Nilotic form 4 groups. It was clearly seen that the link between the individual of the Nilotic is quite weak and some of them linked to the Nubian. The results of thestudy offer useful information about some Sudanese goat breeds

    2016 EMBO Chemical Biology Conference

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    From August 31st- September 3rd the biennual EMBO Chemical Biology conference, hosted by the European Molecular Biology Laboratory (EMBL) in Heidelberg took place. The conference series has earned a well-deserved reputation as one of the finest meetings representing this discipline of life science research. A feature of this EMBO meeting is the consistency of the venue (EMBL is in a delightful location after all) and the organisers (Maja Kohn, John Overington and Carsten Schultz). This ensures familiarity and high complementarity with prior meetings. Indeed, a policy of the organising committee is that no speaker can be talk more than once so one should choose their opportunity wisely.The typical format was adopted where the conference is divided into sections based on topic and talks were a mixture of 4 keynote speakers and 38 speakers, the latter being invited or selected from abstracts. Almost 200 posters were also displayed throughout the meetin

    Design and synthesis of selective ligands for the FK506-binding protein 51

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    Isolation of Jatropha Curcas Seeds Isolectins with Variable Affinity for Human and Animal Blood Types

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    Background: Lectins are carbohydrate-binding protein which agglutinate glycoconjugates in a reversible way, they are with wide applications in biological and medical sciences. Jatropha curcas belongs to the family euphorbiaceae and is distributed in many tropical and subtropical countries. The toxicity of this plant is known for long ago and has been attributed to several components among which is a protein called curcin. Methods: Jatropha curcas seeds were pulverized and protein was extracted with suitable buffer. Protein extract thus obtained had undergone successive protein precipitations by salting-out using (NH4)2SO4 (AS) at 40, 60, and 80% saturations. Lectin activity was detected by hemagglutination method using human- and animal blood types. AS-precipitated protein fractions that possess lectin activity were tested for their antimicrobial activity against the pathogenic Staphylococcus aureus, Escherichia coli, Bacillus aueras, and Candida albicans. Results: At least three isolectins (Lec40, Lec60, and Lec80) were detected by hemagglutination (HA) and isolated by AS fractionation from the crude Jatropha curcas seed extract (CExt). The isolectins exhibited different tendency toward human and animal blood types. None of the isolectins could inhibit any of the used bacterial strains and Candida albicans. Conclusions: In this study, though the detected lectins resemble their counterpart legume lectins, they, however, showed apparently unique and variable behavior toward human and animal blood types. Which might emphasize on the need for further structural analysis on the affinity sites of these proteins. Keywords: Jatropha curcas; euphorbiaceae; lectin; hemagglutination; antimicrobial activit

    Selective Inhibition of the Mitochondrial Permeability Transition Pore Protects against Neurodegeneration in Experimental Multiple Sclerosis

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    The mitochondrial permeability transition pore is a recognized drug target for neurodegenerative conditions such as multiple sclerosis and for ischemia-reperfusion injury in the brain and heart. The peptidylprolyl isomerase, cyclophilin D (CypD, PPIF), is a positive regulator of the pore, and genetic downregulation or knock-out improves outcomes in disease models. Current inhibitors of peptidylprolyl isomerases show no selectivity between the tightly conserved cyclophilin paralogs and exhibit significant off-target effects, immunosuppression, and toxicity. We therefore designed and synthesized a new mitochondrially targeted CypD inhibitor, JW47, using a quinolinium cation tethered to cyclosporine. X-ray analysis was used to validate the design concept, and biological evaluation revealed selective cellular inhibition of CypD and the permeability transition pore with reduced cellular toxicity compared with cyclosporine. In an experimental autoimmune encephalomyelitis disease model of neurodegeneration in multiple sclerosis, JW47 demonstrated significant protection of axons and improved motor assessments with minimal immunosuppression. These findings suggest that selective CypD inhibition may represent a viable therapeutic strategy for MS and identify quinolinium as a mitochondrial targeting group for <i>in vivo</i> use

    1,4‐Pyrazolyl‐Containing SAFit‐Analogues are Selective FKBP51 Inhibitors With Improved Ligand Efficiency and Drug‐Like Profile

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    The FK506 binding protein 51 (FKBP51) is an appealing drug target due to its role in several diseases such as depression, anxiety, chronic pain and obesity. Towards this, selectivity versus the close homolog FKBP52 is essential. However, currently available FKBP51‐selective ligands such as SAFit2 are too large and lack drug‐like properties. Here, we present a structure activity relationship (SAR) analysis of the pipecolic ester moiety of SAFit1 and SAFit2, which culminated in the discovery of the 1,4‐pyrazolyl derivative 23 d, displaying a binding affinity of 0.077 μM for FKBP51, reduced molecular weight (541.7 g/mol), lower hydrophobicity (cLogP=3.72) and higher ligand efficiency (LE=0.25). Cocrystal structures revealed the importance of the 1,4‐ and 1,3,4‐ substitution patterns of the pyrazole ring versus the 1,4,5 arrangement
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