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Photodynamic Molecular Beacons Triggered by MMP-2 and MMP-9: Influence of the Distance Between Photosensitizer and Quencher onto Photophysical Properties and Enzymatic Activation

Identifieur interne : 000A12 ( Main/Merge ); précédent : 000A11; suivant : 000A13

Photodynamic Molecular Beacons Triggered by MMP-2 and MMP-9: Influence of the Distance Between Photosensitizer and Quencher onto Photophysical Properties and Enzymatic Activation

Auteurs : M. Verhille [France] ; H. Benachour [France] ; A. Ibrahim [France] ; M. Achard [France] ; P. Arnoux [France] ; M. Barberi-Heyob [France] ; J.-C. Andre [France] ; X. Allonas [France] ; F. Baros [France] ; R. Vanderesse [France] ; C. Frochot [France]

Source :

RBID : Pascal:13-0074080

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English descriptors

Abstract

Angiogenesis is a key step in the tumoral progression process. It is characterized by an over-expression of a number of matrix metalloproteinases (MMP). Among these MMPs, gelatinases (MMP-2 and MMP-9) are known to play a critical role in tumor angiogenesis and the growth of many cancers. Photodynamic Molecular Beacons (PMB) can be designed for cancer treatment by associating a chlorin-like photosensitizer and a black hole quencher linked by a gelatinase substrate peptide with the aim of silencing photosensitizer toxicity in non-targeted cells and restore its toxicity only in surrounding gelatinases. This article provides a report on the synthesis and photophysical and biochemical studies of new families of PMB, using tetraphenylchlorin and a black hole quencher as a donor-acceptor pair, and MMP specific sequence (H-Gly-Pro-Leu-Gly-Ile-Ala-Gly-Gln-Lys-OH or H-Pro-Leu-Gly-Leu-OH) to keep them in close proximity. Different spacers were used to evaluate the influence of the distance between the photosensitizer and the quencher on the photophysical properties and enzymatic activation of the PMB. Time-resolved quenching experiments were performed and FRET energy transfer could be observed. Photosensitizers' triplet state band in transient absorption disappears in PMB. However, even if both MMP-2 and MMP-9 were found to efficiently cleave the peptide alone, no cleavage was observed for all PMB. Further studies would be required to assess the ability of the PMB constructs to retain the sensitivity of the peptide linker to be cleaved by matrix metalloproteinases.

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Pascal:13-0074080

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<s2>Nancy, 54000</s2>
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<region type="region" nuts="2">Grand Est</region>
<region type="old region" nuts="2">Lorraine (région)</region>
</placeName>
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</author>
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<s3>FRA</s3>
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<placeName>
<region type="region" nuts="2">Grand Est</region>
<region type="old region" nuts="2">Lorraine (région)</region>
</placeName>
<orgName type="university">Université de Lorraine</orgName>
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<sZ>2 aut.</sZ>
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<placeName>
<region type="region" nuts="2">Grand Est</region>
<region type="old region" nuts="2">Lorraine (région)</region>
</placeName>
</affiliation>
</author>
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<name sortKey="Ibrahim, A" sort="Ibrahim, A" uniqKey="Ibrahim A" first="A." last="Ibrahim">A. Ibrahim</name>
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<inist:fA14 i1="07">
<s1>Université de Haute Alsace, Departement de Photochimie Générale, UMR CNRS 7525</s1>
<s2>Mulhouse, 68100</s2>
<s3>FRA</s3>
<sZ>3 aut.</sZ>
<sZ>8 aut.</sZ>
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<country>France</country>
<placeName>
<region type="region" nuts="2">Grand Est</region>
<region type="old region" nuts="2">Alsace (région administrative)</region>
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</affiliation>
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<name sortKey="Achard, M" sort="Achard, M" uniqKey="Achard M" first="M." last="Achard">M. Achard</name>
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<inist:fA14 i1="03">
<s1>Université de Lorraine, Laboratoire de Chimie Physique Macromoléculaire (LCPM), UMR CNRS 7568</s1>
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<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName>
<region type="region" nuts="2">Grand Est</region>
<region type="old region" nuts="2">Lorraine (région)</region>
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<region type="region" nuts="2">Grand Est</region>
<region type="old region" nuts="2">Lorraine (région)</region>
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<s1>Université de Lorraine, Laboratoire Réactions et Génie des Procédés (LRGP), UPR 3349</s1>
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<sZ>1 aut.</sZ>
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<country>France</country>
<placeName>
<region type="region" nuts="2">Grand Est</region>
<region type="old region" nuts="2">Lorraine (région)</region>
</placeName>
<orgName type="university">Université de Lorraine</orgName>
</affiliation>
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<inist:fA14 i1="02">
<s1>CNRS, LRGP, UPR 3349</s1>
<s2>Nancy, 54000</s2>
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<sZ>5 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>9 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName>
<region type="region" nuts="2">Grand Est</region>
<region type="old region" nuts="2">Lorraine (région)</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Barberi Heyob, M" sort="Barberi Heyob, M" uniqKey="Barberi Heyob M" first="M." last="Barberi-Heyob">M. Barberi-Heyob</name>
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<inist:fA14 i1="05">
<s1>Université de Lorraine, Centre de Recherche en Automatique de Nancy (CRAN), UMR 7039, Campus Science, BP 70239</s1>
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<s3>FRA</s3>
<sZ>2 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>11 aut.</sZ>
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<country>France</country>
<placeName>
<region type="region" nuts="2">Grand Est</region>
<region type="old region" nuts="2">Lorraine (région)</region>
</placeName>
<orgName type="university">Université de Lorraine</orgName>
</affiliation>
<affiliation wicri:level="3">
<inist:fA14 i1="06">
<s1>CNRS, CRAN, UMR CNRS 7039, Centre Alexis Vautrin</s1>
<s2>Vandœuvre-lès-Nancy, 54500</s2>
<s3>FRA</s3>
<sZ>2 aut.</sZ>
<sZ>6 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName>
<region type="region" nuts="2">Grand Est</region>
<region type="old region" nuts="2">Lorraine (région)</region>
</placeName>
</affiliation>
<affiliation wicri:level="1">
<inist:fA14 i1="08">
<s1>GDR CNRS 3049 "Médicaments Photoactivables-Photochimiothérapie (PHOTOMED)"</s1>
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<sZ>6 aut.</sZ>
<sZ>10 aut.</sZ>
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</inist:fA14>
<country>France</country>
<wicri:noRegion>GDR CNRS 3049 "Médicaments Photoactivables-Photochimiothérapie (PHOTOMED)"</wicri:noRegion>
<wicri:noRegion>GDR CNRS 3049 "Médicaments Photoactivables-Photochimiothérapie (PHOTOMED)"</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3">
<inist:fA14 i1="09">
<s1>Centre Alexis Vautrin, CRLCC, avenue de Bourgogne</s1>
<s2>Vandœuvre-lès-Nancy, 54511</s2>
<s3>FRA</s3>
<sZ>6 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName>
<region type="region" nuts="2">Grand Est</region>
<region type="old region" nuts="2">Lorraine (région)</region>
</placeName>
</affiliation>
</author>
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<name sortKey="Andre, J C" sort="Andre, J C" uniqKey="Andre J" first="J.-C." last="Andre">J.-C. Andre</name>
<affiliation wicri:level="4">
<inist:fA14 i1="01">
<s1>Université de Lorraine, Laboratoire Réactions et Génie des Procédés (LRGP), UPR 3349</s1>
<s2>Nancy, 54000</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName>
<region type="region" nuts="2">Grand Est</region>
<region type="old region" nuts="2">Lorraine (région)</region>
</placeName>
<orgName type="university">Université de Lorraine</orgName>
</affiliation>
<affiliation wicri:level="3">
<inist:fA14 i1="02">
<s1>CNRS, LRGP, UPR 3349</s1>
<s2>Nancy, 54000</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>9 aut.</sZ>
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<country>France</country>
<placeName>
<region type="region" nuts="2">Grand Est</region>
<region type="old region" nuts="2">Lorraine (région)</region>
</placeName>
</affiliation>
</author>
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<name sortKey="Allonas, X" sort="Allonas, X" uniqKey="Allonas X" first="X." last="Allonas">X. Allonas</name>
<affiliation wicri:level="3">
<inist:fA14 i1="07">
<s1>Université de Haute Alsace, Departement de Photochimie Générale, UMR CNRS 7525</s1>
<s2>Mulhouse, 68100</s2>
<s3>FRA</s3>
<sZ>3 aut.</sZ>
<sZ>8 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName>
<region type="region" nuts="2">Grand Est</region>
<region type="old region" nuts="2">Alsace (région administrative)</region>
</placeName>
</affiliation>
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<name sortKey="Baros, F" sort="Baros, F" uniqKey="Baros F" first="F." last="Baros">F. Baros</name>
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<inist:fA14 i1="01">
<s1>Université de Lorraine, Laboratoire Réactions et Génie des Procédés (LRGP), UPR 3349</s1>
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<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName>
<region type="region" nuts="2">Grand Est</region>
<region type="old region" nuts="2">Lorraine (région)</region>
</placeName>
<orgName type="university">Université de Lorraine</orgName>
</affiliation>
<affiliation wicri:level="3">
<inist:fA14 i1="02">
<s1>CNRS, LRGP, UPR 3349</s1>
<s2>Nancy, 54000</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>9 aut.</sZ>
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<country>France</country>
<placeName>
<region type="region" nuts="2">Grand Est</region>
<region type="old region" nuts="2">Lorraine (région)</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Vanderesse, R" sort="Vanderesse, R" uniqKey="Vanderesse R" first="R." last="Vanderesse">R. Vanderesse</name>
<affiliation wicri:level="4">
<inist:fA14 i1="03">
<s1>Université de Lorraine, Laboratoire de Chimie Physique Macromoléculaire (LCPM), UMR CNRS 7568</s1>
<s2>Nancy, 54000</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName>
<region type="region" nuts="2">Grand Est</region>
<region type="old region" nuts="2">Lorraine (région)</region>
</placeName>
<orgName type="university">Université de Lorraine</orgName>
</affiliation>
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<inist:fA14 i1="04">
<s1>CNRS, LCPM, UMR CNRS 7568</s1>
<s2>Nancy, 54000</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName>
<region type="region" nuts="2">Grand Est</region>
<region type="old region" nuts="2">Lorraine (région)</region>
</placeName>
</affiliation>
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<s1>GDR CNRS 3049 "Médicaments Photoactivables-Photochimiothérapie (PHOTOMED)"</s1>
<s3>FRA</s3>
<sZ>6 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>France</country>
<wicri:noRegion>GDR CNRS 3049 "Médicaments Photoactivables-Photochimiothérapie (PHOTOMED)"</wicri:noRegion>
<wicri:noRegion>GDR CNRS 3049 "Médicaments Photoactivables-Photochimiothérapie (PHOTOMED)"</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Frochot, C" sort="Frochot, C" uniqKey="Frochot C" first="C." last="Frochot">C. Frochot</name>
<affiliation wicri:level="4">
<inist:fA14 i1="01">
<s1>Université de Lorraine, Laboratoire Réactions et Génie des Procédés (LRGP), UPR 3349</s1>
<s2>Nancy, 54000</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName>
<region type="region" nuts="2">Grand Est</region>
<region type="old region" nuts="2">Lorraine (région)</region>
</placeName>
<orgName type="university">Université de Lorraine</orgName>
</affiliation>
<affiliation wicri:level="4">
<inist:fA14 i1="05">
<s1>Université de Lorraine, Centre de Recherche en Automatique de Nancy (CRAN), UMR 7039, Campus Science, BP 70239</s1>
<s2>Vandœuvre-lès-Nancy, 54500</s2>
<s3>FRA</s3>
<sZ>2 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName>
<region type="region" nuts="2">Grand Est</region>
<region type="old region" nuts="2">Lorraine (région)</region>
</placeName>
<orgName type="university">Université de Lorraine</orgName>
</affiliation>
<affiliation wicri:level="1">
<inist:fA14 i1="08">
<s1>GDR CNRS 3049 "Médicaments Photoactivables-Photochimiothérapie (PHOTOMED)"</s1>
<s3>FRA</s3>
<sZ>6 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>France</country>
<wicri:noRegion>GDR CNRS 3049 "Médicaments Photoactivables-Photochimiothérapie (PHOTOMED)"</wicri:noRegion>
<wicri:noRegion>GDR CNRS 3049 "Médicaments Photoactivables-Photochimiothérapie (PHOTOMED)"</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series>
<title level="j" type="main">Current medicinal chemistry</title>
<title level="j" type="abbreviated">Curr. med. chem.</title>
<idno type="ISSN">0929-8673</idno>
<imprint>
<date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt>
<title level="j" type="main">Current medicinal chemistry</title>
<title level="j" type="abbreviated">Curr. med. chem.</title>
<idno type="ISSN">0929-8673</idno>
</seriesStmt>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Activation</term>
<term>Biological activity</term>
<term>Gelatinase A</term>
<term>Gelatinase B</term>
<term>Photodynamic therapy</term>
<term>Photosensitizer</term>
<term>Targeting</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr">
<term>Gelatinase A</term>
<term>Gelatinase B</term>
<term>Photosensibilisant</term>
<term>Activation</term>
<term>Activité biologique</term>
<term>Photothérapie dynamique</term>
<term>Ciblage</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">Angiogenesis is a key step in the tumoral progression process. It is characterized by an over-expression of a number of matrix metalloproteinases (MMP). Among these MMPs, gelatinases (MMP-2 and MMP-9) are known to play a critical role in tumor angiogenesis and the growth of many cancers. Photodynamic Molecular Beacons (PMB) can be designed for cancer treatment by associating a chlorin-like photosensitizer and a black hole quencher linked by a gelatinase substrate peptide with the aim of silencing photosensitizer toxicity in non-targeted cells and restore its toxicity only in surrounding gelatinases. This article provides a report on the synthesis and photophysical and biochemical studies of new families of PMB, using tetraphenylchlorin and a black hole quencher as a donor-acceptor pair, and MMP specific sequence (H-Gly-Pro-Leu-Gly-Ile-Ala-Gly-Gln-Lys-OH or H-Pro-Leu-Gly-Leu-OH) to keep them in close proximity. Different spacers were used to evaluate the influence of the distance between the photosensitizer and the quencher on the photophysical properties and enzymatic activation of the PMB. Time-resolved quenching experiments were performed and FRET energy transfer could be observed. Photosensitizers' triplet state band in transient absorption disappears in PMB. However, even if both MMP-2 and MMP-9 were found to efficiently cleave the peptide alone, no cleavage was observed for all PMB. Further studies would be required to assess the ability of the PMB constructs to retain the sensitivity of the peptide linker to be cleaved by matrix metalloproteinases.</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>France</li>
</country>
<region>
<li>Alsace (région administrative)</li>
<li>Grand Est</li>
<li>Lorraine (région)</li>
</region>
<orgName>
<li>Université de Lorraine</li>
</orgName>
</list>
<tree>
<country name="France">
<region name="Grand Est">
<name sortKey="Verhille, M" sort="Verhille, M" uniqKey="Verhille M" first="M." last="Verhille">M. Verhille</name>
</region>
<name sortKey="Achard, M" sort="Achard, M" uniqKey="Achard M" first="M." last="Achard">M. Achard</name>
<name sortKey="Achard, M" sort="Achard, M" uniqKey="Achard M" first="M." last="Achard">M. Achard</name>
<name sortKey="Allonas, X" sort="Allonas, X" uniqKey="Allonas X" first="X." last="Allonas">X. Allonas</name>
<name sortKey="Andre, J C" sort="Andre, J C" uniqKey="Andre J" first="J.-C." last="Andre">J.-C. Andre</name>
<name sortKey="Andre, J C" sort="Andre, J C" uniqKey="Andre J" first="J.-C." last="Andre">J.-C. Andre</name>
<name sortKey="Arnoux, P" sort="Arnoux, P" uniqKey="Arnoux P" first="P." last="Arnoux">P. Arnoux</name>
<name sortKey="Arnoux, P" sort="Arnoux, P" uniqKey="Arnoux P" first="P." last="Arnoux">P. Arnoux</name>
<name sortKey="Barberi Heyob, M" sort="Barberi Heyob, M" uniqKey="Barberi Heyob M" first="M." last="Barberi-Heyob">M. Barberi-Heyob</name>
<name sortKey="Barberi Heyob, M" sort="Barberi Heyob, M" uniqKey="Barberi Heyob M" first="M." last="Barberi-Heyob">M. Barberi-Heyob</name>
<name sortKey="Barberi Heyob, M" sort="Barberi Heyob, M" uniqKey="Barberi Heyob M" first="M." last="Barberi-Heyob">M. Barberi-Heyob</name>
<name sortKey="Barberi Heyob, M" sort="Barberi Heyob, M" uniqKey="Barberi Heyob M" first="M." last="Barberi-Heyob">M. Barberi-Heyob</name>
<name sortKey="Baros, F" sort="Baros, F" uniqKey="Baros F" first="F." last="Baros">F. Baros</name>
<name sortKey="Baros, F" sort="Baros, F" uniqKey="Baros F" first="F." last="Baros">F. Baros</name>
<name sortKey="Benachour, H" sort="Benachour, H" uniqKey="Benachour H" first="H." last="Benachour">H. Benachour</name>
<name sortKey="Benachour, H" sort="Benachour, H" uniqKey="Benachour H" first="H." last="Benachour">H. Benachour</name>
<name sortKey="Frochot, C" sort="Frochot, C" uniqKey="Frochot C" first="C." last="Frochot">C. Frochot</name>
<name sortKey="Frochot, C" sort="Frochot, C" uniqKey="Frochot C" first="C." last="Frochot">C. Frochot</name>
<name sortKey="Frochot, C" sort="Frochot, C" uniqKey="Frochot C" first="C." last="Frochot">C. Frochot</name>
<name sortKey="Ibrahim, A" sort="Ibrahim, A" uniqKey="Ibrahim A" first="A." last="Ibrahim">A. Ibrahim</name>
<name sortKey="Vanderesse, R" sort="Vanderesse, R" uniqKey="Vanderesse R" first="R." last="Vanderesse">R. Vanderesse</name>
<name sortKey="Vanderesse, R" sort="Vanderesse, R" uniqKey="Vanderesse R" first="R." last="Vanderesse">R. Vanderesse</name>
<name sortKey="Vanderesse, R" sort="Vanderesse, R" uniqKey="Vanderesse R" first="R." last="Vanderesse">R. Vanderesse</name>
<name sortKey="Verhille, M" sort="Verhille, M" uniqKey="Verhille M" first="M." last="Verhille">M. Verhille</name>
<name sortKey="Verhille, M" sort="Verhille, M" uniqKey="Verhille M" first="M." last="Verhille">M. Verhille</name>
<name sortKey="Verhille, M" sort="Verhille, M" uniqKey="Verhille M" first="M." last="Verhille">M. Verhille</name>
</country>
</tree>
</affiliations>
</record>

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