Roba MOUMNE

@article{Denefle:2016,
title = {Thrombospondin-1 Mimetic Agonist Peptides Induce Selective Death in Tumor Cells: Design, Synthesis, and Structure-Activity Relationship Studies},
author = {T Den\`{e}fle and H Boullet and L Herbi and C Newton and A -C Martinez-Torres and A Guez and E Pramil and C Quiney and M Pourcelot and M D Levasseur and E Lard\'{e} and R Moumn\'{e} and F -X Ogi and P Grondin and H Merle-Beral and O Lequin and S A Susin and P Karoyan},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84988735397&doi=10.1021%2facs.jmedchem.6b00781&partnerID=40&md5=56822fdf1d99463527e7e00830952716},
doi = {10.1021/acs.jmedchem.6b00781},
year = {2016},
date = {2016-01-01},
journal = {Journal of Medicinal Chemistry},
volume = {59},
number = {18},
pages = {8412--8421},
abstract = {Thrombospondin-1 (TSP-1) is a glycoprotein considered as a key actor within the tumor microenvironment. Its binding to CD47, a cell surface receptor, triggers programmed cell death. Previous studies allowed the identification of 4N1K decapeptide derived from the TSP-1/CD47 binding epitope. Here, we demonstrate that this peptide is able to induce selective apoptosis of various cancer cell lines while sparing normal cells. A structure-activity relationship study led to the design of the first serum stable TSP-1 mimetic agonist peptide able to trigger selective programmed cell death (PCD) of at least lung, breast, and colorectal cancer cells. Altogether, these results will be of valuable interest for further investigation in the design of potent CD47 agonist peptides, opening new perspectives for the development of original anticancer therapies. © 2016 American Chemical Society.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{Martinez-Torres:2015,
title = {CD47 Agonist Peptides Induce Programmed Cell Death in Refractory Chronic Lymphocytic Leukemia B Cells via PLCγ1 Activation: Evidence from Mice and Humans},
author = {A -C Martinez-Torres and C Quiney and T Attout and H Boullet and L Herbi and L Vela and S Barbier and D Chateau and E Chapiro and F Nguyen-Khac and F Davi and M Le Garff-Tavernier and R Moumn\'{e} and M Sarfati and P Karoyan and H Merle-B\'{e}ral and P Launay and S A Susin},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84926512944&doi=10.1371%2fjournal.pmed.1001796&partnerID=40&md5=d6d0c23386f4e276919f9360d0bf5e83},
doi = {10.1371/journal.pmed.1001796},
year = {2015},
date = {2015-01-01},
journal = {PLoS Medicine},
volume = {12},
number = {3},
abstract = {Chronic lymphocytic leukemia (CLL), the most common adulthood leukemia, is characterized by the accumulation of abnormal CD5+ B lymphocytes, which results in a progressive failure of the immune system. Despite intense research efforts, drug resistance remains a major cause of treatment failure in CLL, particularly in patients with dysfunctional TP53. The objective of our work was to identify potential approaches that might overcome CLL drug refractoriness by examining the pro-apoptotic potential of targeting the cell surface receptor CD47 with serum-stable agonist peptides. In peripheral blood samples collected from 80 patients with CLL with positive and adverse prognostic features, we performed in vitro genetic and molecular analyses that demonstrate that the targeting of CD47 with peptides derived from the C-terminal domain of thrombospondin-1 efficiently kills the malignant CLL B cells, including those from high-risk individuals with a dysfunctional TP53 gene, while sparing the normal T and B lymphocytes from the CLL patients. Further studies reveal that the differential response of normal B lymphocytes, collected from 20 healthy donors, and leukemic B cells to CD47 peptide targeting results from the sustained activation in CLL B cells of phospholipase C gamma-1 (PLCγ1), a protein that is significantly over-expressed in CLL. Once phosphorylated at tyrosine 783, PLCγ1 enables a Ca2+-mediated, caspase-independent programmed cell death (PCD) pathway that is not down-modulated by the lymphocyte microenvironment. Accordingly, down-regulation of PLCγ1 or pharmacological inhibition of PLCγ1 phosphorylation abolishes CD47-mediated killing. Additionally, in a CLL-xenograft model developed in NOD/scid gamma mice, we demonstrate that the injection of CD47 agonist peptides reduces tumor burden without inducing anemia or toxicity in blood, liver, or kidney. The limitations of our study are mainly linked to the affinity of the peptides targeting CD47, which might be improved to reach the standard requirements in drug development, and the lack of a CLL animal model that fully mimics the human disease. Our work provides substantial progress in (i) the development of serum-stable CD47 agonist peptides that are highly effective at inducing PCD in CLL, (ii) the understanding of the molecular events regulating a novel PCD pathway that overcomes CLL apoptotic avoidance, (iii) the identification of PLCγ1 as an over-expressed protein in CLL B cells, and (iv) the description of a novel peptide-based strategy against CLL. © 2015 Martinez-Torres et al.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{Caumes:2013,
title = {Homooligomers of substituted prolines and β-prolines: Syntheses and secondary structure investigation},
author = {C Caumes and N Delsuc and R B Azza and I Correia and F Chemla and F Ferreira and L Carlier and A P Luna and R Moumn\'{e} and O Lequin and P Karoyan},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84876740702&doi=10.1039%2fc3nj00127j&partnerID=40&md5=dbda08d94a12bcb6b260393c90dd6af4},
doi = {10.1039/c3nj00127j},
year = {2013},
date = {2013-01-01},
journal = {New Journal of Chemistry},
volume = {37},
number = {5},
pages = {1312--1319},
abstract = {Homooligomers of enantiomerically pure (2S,3R)-3-methyl-proline, (3R,4R)-4-methyl-β-proline and (3R,4S)-3,4-dimethyl-β-proline were synthesized and studied using circular dichroism (CD) in water, methanol and propanol and using NMR in water. Changes in the far-UV CD spectrum were observed from dimers to hexamers, but little change was observed from hexamers to octa- or nonamers, both in water and methanol. CD and NMR data allowed us to conclude that oligomers of 3-substituted prolines with more than six residues adopt a characteristic PPII secondary structure both in water and aliphatic alcohols. Oligomers of (3R,4R)-4-methyl-β-proline bear the same CD signature as non-substituted β-proline oligomers, suggesting that substitution at position 3 is not sufficient to reduce conformational heterogeneity in β-proline oligomers. In the case of 3,4-disubstituted-β-proline oligomers, an atypical signature with an extra negative band at around 225 nm was observed, together with a concentration dependent CD spectrum indicating association properties. Nevertheless, NMR studies of 13C labelled oligomers of 3,4-disubstituted-β-prolines revealed a complex mixture of cis-trans conformers even for longer oligomers. © 2913 The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{Mothes:2013,
title = {3-substituted prolines: From synthesis to structural applications, from peptides to foldamers},
author = {C Mothes and C Caumes and A Guez and H Boullet and T Gendrineau and S Darses and N Delsuc and R Moumn\'{e} and B Oswald and O Lequin and P Karoyan},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84874605320&doi=10.3390%2fmolecules18022307&partnerID=40&md5=05828aecf601bf07f9a0a6a3fec4e28c},
doi = {10.3390/molecules18022307},
year = {2013},
date = {2013-01-01},
journal = {Molecules},
volume = {18},
number = {2},
pages = {2307--2327},
abstract = {Among the twenty natural proteinogenic amino acids, proline is unique as its secondary amine forms a tertiary amide when incorporated into biopolymers, thus preventing hydrogen bond formation. Despite the lack of hydrogen bonds and thanks to conformational restriction of flexibility linked to the pyrrolidine ring, proline is able to stabilize peptide secondary structures such as -turns or polyproline helices. These unique conformational properties have aroused a great interest in the development of proline analogues. Among them, proline chimeras are tools combining the proline restriction of flexibility together with the information brought by natural amino acids side chains. This review will focus on the chemical syntheses of 3-substituted proline chimeras of potential use for peptide syntheses and as potential use as tools for SAR studies of biologically active peptides and the development of secondary structure mimetics. Their influence on peptide structure will be briefly described. © 2013 by the authors.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}