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Paul S Donnelly - One of the best experts on this subject based on the ideXlab platform.

Rodney J Hicks - One of the best experts on this subject based on the ideXlab platform.

Carleen Cullinane - One of the best experts on this subject based on the ideXlab platform.

Rachel Codd - One of the best experts on this subject based on the ideXlab platform.

  • Analogues of <B>DesferrioxamineB> B (DFOB) with new properties and new functions generated using precursor-directed Biosynthesis
    BioMetals, 2019
    Co-Authors: Thomas J Telfer, Michael P Gotsbacher, Tomas Richardson-sanchez, Kate P. Nolan, William Tieu, Rachel Codd
    Abstract:

    <B>DesferrioxamineB> B (DFOB) is a siderophore native to Streptomyces pilosus Biosynthesised By the DesABCD enzyme cluster as a high affinity Fe(III) chelator. Although DFOB has a long clinical history for the treatment of chronic iron overload, limitations encourage the development of new analogues. This review descriBes a recent Body of work that has used precursor-directed Biosynthesis (PDB) to access new DFOB analogues. PDB exploits the native Biosynthetic machinery of a producing organism in culture medium augmented with non-native suBstrates that compete against native suBstrates during metaBolite assemBly. The method allows access to analogues of natural products using Benign methods, compared to multistep organic synthesis. The disadvantages of PDB are the production of metaBolites in low yield and the need to purify complex mixtures. Streptomyces pilosus medium was supplemented with different types of non-native diamine suBstrates to compete against native 1,5-diaminopentane to generate DFOB analogues containing alkene Bonds, fluorine atoms, ether or thioether functional groups, or a disulfide Bond. All analogues retained function as Fe(III) chelators and have properties that could Broaden the utility of DFOB. These PDB studies have also added knowledge to the understanding of DFOB Biosynthesis.

  • Fluorinated Analogues of <B>DesferrioxamineB> B from Precursor-Directed Biosynthesis Provide New Insight into the Capacity of DesBCD.
    ACS chemical biology, 2018
    Co-Authors: Thomas J Telfer, Rachel Codd
    Abstract:

    The siderophore <B>DesferrioxamineB> B (DFOB, 1) native to Streptomyces pilosus is Biosynthesized By the DesABCD enzyme cluster. DesA-mediated decarBoxylation of l-lysine gives 1,5-diaminopentane (DP) for processing By DesBCD. S. pilosus culture medium was supplemented with rac-1,4-diamino-2-fluoroButane (rac-FDB) to compete against DP to generate fluorinated analogues of DFOB, as agents of potential clinical interest. LC-MS/MS analysis identified fluorinated analogues of DFOB with one, two, or three DP units (Binary notation: 0) exchanged for one (DFOA-F1[001] (2), DFOA-F1[010] (3), DFOA-F1[100] (4)), two (DFOA-F2[011] (5), DFOA-F2[110] (6), DFOA-F2[101] (7)), or three (DFOA-F3[111] (8)) rac-FDB units (Binary notation: 1). The two sets of constitutional isomers 2–4 and 5–7 arose from the position of the suBstrates in the N-acetyl, internal, or amine-containing regions of the DFOB trimer. N-Acetylated fluorinated DFOB analogues were formed where the rac-FDB suBstrate was positioned in the amine region (e.g., N...

  • advances in the chemical Biology of <B>DesferrioxamineB> B
    ACS Chemical Biology, 2017
    Co-Authors: Rachel Codd, Tomas Richardsonsanchez, Thomas J Telfer, Michael P Gotsbacher
    Abstract:

    <B>DesferrioxamineB> B (DFOB) was discovered in the late 1950s as a hydroxamic acid metaBolite of the soil Bacterium Streptomyces pilosus. The exquisite affinity of DFOB for Fe(III) identified its potential for removing excess iron from patients with transfusion-dependent hemogloBin disorders. Many studies have used semisynthetic chemistry to produce DFOB adducts with new properties and Broad-ranging functions. More recent approaches in chemical Biology have revealed some nuances of DFOB Biosynthesis and discovered new DFOB-derived drugs and radiometal imaging agents. The current and potential applications of DFOB continue to inspire a rich Body of chemical Biology research focused on this Bacterial metaBolite.

  • mixing up the pieces of the <B>DesferrioxamineB> B jigsaw defines the Biosynthetic sequence catalyzed By desd
    ACS Chemical Biology, 2016
    Co-Authors: Thomas J Telfer, Michael P Gotsbacher, Rachel Codd
    Abstract:

    Late-stage assemBly of the trimeric linear siderophore <B>DesferrioxamineB> B (DFOB) native to Streptomyces pilosus involves two DesD-catalyzed condensation reactions Between one N-acetyl-N-hydroxy-1,5-diaminopentane (AHDP) unit and two N-succinyl-N-hydroxy-1,5-diaminopentane (SHDP) units. AHDP and SHDP are products of DesBC-catalyzed reactions of the native diamine suBstrate 1,5-diaminopentane (DP). The sequence of DesD-catalyzed DFOB Biosynthesis was delineated By analyzing the distriBution of DFOB analogues and dimeric precursors assemBled By S. pilosus in medium containing 1,4-diamino-2(E)-Butene (E-DBE). Seven unsaturated DFOB analogues were produced that were partially resolved By liquid chromatography (LC). Mass spectrometry (MS) measurements reported on the comBination of E-DBE- and DP-derived suBstrates in each trimer (uDFOA1 series, 1:2; uDFOA2 series, 2:1; uDFOA3, 3:0). MS/MS fragmentation patterns reported on the aBsolute position of the suBstrate derivative at the N-acetylated terminus, the intern...

  • coordinate Bond dependent solid phase organic synthesis of Biotinylated <B>DesferrioxamineB> B a new route for metal specific proBes
    Chemical Communications, 2012
    Co-Authors: Tulip Lifa, Najwa Ejje, Rachel Codd
    Abstract:

    <B>DesferrioxamineB> B (DFOB) was Biotinylated at the pendant amine using solid-phase organic synthesis (SPOS) on a matrix used conventionally for metal affinity chromatography. The strength of the DFOB-matrix coordinate Bonds was functionally equivalent to a covalent Bond which underpinned the veracity of the SPOS format. After washing excess reagents, Biotin-DFOB was eluted from the matrix with water at pH 6.

Stacey E Rudd - One of the best experts on this subject based on the ideXlab platform.