English
norskBlar i forfatter "Haug, Bengt Erik"
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Aldol condensations on a 3-alkylidene-2,5-diketopiperazine - synthesis of two marine natural products
(Journal article; Tidsskriftartikkel; Peer reviewed, 2018-06)The synthesis of two marine natural products containing a 3-alkylidene-6-arylidene-2,5-diketopiperazine scaffold by employing two consecutive aldol condensations starting with 1,4-diacetyl-2,5-diketopiperazine is reported. The target compounds contain a phenol or an imidazole group as aryl substituents, respectively, and suitable conditions for the aldol condensation of 1-acyl-3-alkylidene-2,5-dik ... -
A Concise Total Synthesis of Breitfussin A and B
(Journal article; Tidsskriftartikkel; Peer reviewed, 2014) -
Design, synthesis, and biological evaluation of scaffold-based tripeptidomimetic antagonists for CXC chemokine receptor 4 (CXCR4)
(Journal article; Tidsskriftartikkel; Peer reviewed, 2014-07-14) -
Influence of chain length on the activity of tripeptidomimetic antagonists for CXC chemokine receptor 4 (CXCR4)
(Journal article; Tidsskriftartikkel; Peer reviewed, 2016-11-21)Here we report a series of close analogues of our recently published scaffold-based tripeptidomimetic CXCR4 antagonists, containing positively charged guanidino groups in R1 and R2, and an aromatic group in R3. While contraction/elongation of the guanidine carrying side chains (R1 and R2) resulted in loss of activity, introduction of bromine in position 1 on the naphth-2-ylmethyl moiety (R3 ... -
Kinase chemodiversity from the Arctic: the breitfussins
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-10-24)In this work, we demonstrate that the indole-oxazole-pyrrole framework of the breitfussin family of natural products is a promising scaffold for kinase inhibition. Six new halogenated natural products, breitfussin C–H (3 – 8) were isolated and characterized from the Arctic, marine hydrozoan Thuiaria breitfussi. The structures of two of the new natural products were also confirmed by total synthesis. ... -
LTX-315: a first-in-class oncolytic peptide that reprograms the tumor microenvironment
(Journal article; Tidsskriftartikkel; Peer reviewed, 2017-05-08)The oncolytic peptide LTX-315, which has been <i>de novo</i> designed based on structure– activity relationship studies of host defense peptides, has the ability to kill human cancer cells and induce specific anticancer immune response when injected locally into tumors established in immunocompetent mice. The oncolytic effect of LTX-315 involves perturbation of plasma membrane and the mitochondria ... -
Oncolytic peptide LTX-315 induces an immune-mediated abscopal effect in a rat sarcoma model
(Journal article; Tidsskriftartikkel; Peer reviewed, 2017-08-17)LTX 315 is an oncolytic peptide with potent immunological properties. In the present study, we demonstrate that intratumoral treatment with LTX-315 resulted in a complete regression and systemic immune response in a rat fibrosarcoma model. The treatment was T-cell dependent, and also resulted in an abscopal effect as demonstrated by the regression of distal non-treated lesions. Significant infiltration ... -
Probing the molecular interactions between CXC chemokine receptor 4 (CXCR4) and an arginine-based tripeptidomimetic antagonist (KRH-1636)
(Journal article; Tidsskriftartikkel; Peer reviewed, 2015-09-23)We here report an experimentally verified binding mode for the known tripeptidomimetic CXCR4 antagonist KRH-1636 (1). A limited SAR study based on the three functionalities of 1 was first conducted, followed by site-directed mutagenesis studies. The receptor mapping showed that both the potency and affinity of 1 were dependent on the transmembrane residues His113, Asp171, Asp262, and His281 and also ... -
Progress toward rationally designed small-molecule peptide and peptidomimetic CXCR4 antagonists
(Journal article; Tidsskriftartikkel; Peer reviewed, 2015-06)Over the last five years, X-ray structures of CXC chemokine receptor 4 (CXCR4) in complex with three different ligands (the small-molecule antagonist IT1t, the polypeptide antagonist CVX15, and the viral chemokine antagonist vMIP-II) have been released. In addition to the inherent scientific value of these specific X-ray structures, they (i) provide a reliable structural ... -
The relative spatial positions of tryptophan and cationic residues in helical membrane-active peptides determines their cytotoxicity
(Journal article; Tidsskriftartikkel; Peer reviewed, 2011-11-04)Background: Tryptophan side chains can influence the binding of amphipathic peptides to biological membranes. <p>Results: The cytotoxic activity of model helical amphipathic peptides was markedly influenced by the positions of tryptophan residues in the sequence. <p>Conclusion: Tryptophan residues located adjacent to a hydrophobic helical portion created the most potent cytotoxic peptides. <p> ... -
Synthesis of a novel tripeptidomimetic scaffold and biological evaluation for CXC chemokine receptor 4 (CXCR4) antagonism
(Journal article; Tidsskriftartikkel; Peer reviewed, 2017-05-17)We here report the preparation of a new 2,6,8-trisubstituted bicyclic tripeptidomimetic scaffold through TFA-mediated cyclization of a linear precursor containing three side chains. The introduction of a triphenylmethyl-protected thiol into carboxylic acid containing building blocks through sulfa Michael additions onto α,β-unsaturated hexafluoroisopropyl esters is described. The stereoselectivity ... -
Total Synthesis of Phorbazole B
(Journal article; Tidsskriftartikkel; Peer reviewed, 2020-10-21)Phorbazoles are polychlorinated heterocyclic secondary metabolites isolated from a marine sponge and several of these natural products have shown inhibitory activity against cancer cells. In this work, a synthesis of the trichlorinated phorbazole B using late stage electrophilic chlorination was developed. The synthesis relied on the use of an oxazole precursor, which was protected with an iodine ... -
Unequivocal structure confirmation of a breitfussin analog by anisotropic NMR measurements
(Journal article; Tidsskriftartikkel; Peer reviewed, 2020-09-21)Structural features of proton-deficient heteroaromatic natural products, such as the breitfussins, can severely complicate their characterization by NMR spectroscopy. For the breitfussins in particular, the constitution of the five-membered oxazole central ring cannot be unequivocally established via conventional NMR methods when the 4′-position is halogenated. The level of difficulty is exacerbated ...
