Brigitte Guérin - Profile on Academia.edu (original) (raw)
Papers by Brigitte Guérin
Radiolabeled BODIPYs: An overview
Porphyrin Science by Women, 2021
Pd‐Catalyzed Sonogashira Cross‐Coupling Reactions of gem ‐Dibromovinyl BODIPY Derivatives
European Journal of Organic Chemistry, 2021
CCDC 2008305: Experimental Crystal Structure Determination
Bifunctional chelates for 64Cu radiolabelling of BBN peptides for PET imaging, a comparative study
The Journal of Nuclear Medicine, 2011
Theranostic potential of a new [64Cu]-radiolabeled R-954 conjugate for kinin B1R positive tumors
The Journal of Nuclear Medicine, 2016
Peptide Science, 2018
Enkephalins are pentapeptidic endogenous ligands that regulate nociception by binding to mu (MOP)... more Enkephalins are pentapeptidic endogenous ligands that regulate nociception by binding to mu (MOP) and delta (DOP) opioid receptors. To further explore the role of the leucine residue of Leu‐enkephalin, 12 peptidomimetic analogs were synthesized by systematically replacing this residue with non‐natural amino acids. The analogs were tested for their ability to bind DOP and MOP. We also investigated the potency of these analogs to inhibit cAMP production and to recruit β‐arrestin 2 via both receptors. We found that replacement of the leucine residue by substituted non‐natural amino acid derivatives of alanine, cycloleucine, or isoleucine was generally well tolerated. By contrast, substituting leucine with homoproline greatly reduced the affinity for DOP and, to a lesser extent, for MOP. Interestingly, when compared to Leu‐enkephalin, analogs containing either aza‐β‐homoleucine or cycloleucine showed a bias toward inhibition of cAMP production through the activation of DOP but not MOP. ...
High Cytotoxic Effect by Combining Copper-64 with a NOTA–Terpyridine Platinum Conjugate
Journal of Medicinal Chemistry, 2021
Terpyridine platinum (TP)-based chemotherapeutic agents target three-dimensional structures on DN... more Terpyridine platinum (TP)-based chemotherapeutic agents target three-dimensional structures on DNA known as G-quadruplexes. We report the rational design and synthesis of a TP conjugate combined with copper-64 (64Cu), the decay characteristics of which include emission of β- and Auger electrons for radiotherapy and β+ particles for positron emission tomography (PET) imaging. The present experimental studies show that the novel [64Cu]Cu-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-TP is stable, permitting selective killing of cancer cells. The antitumor activity of [64Cu]Cu-NOTA-TP at high apparent molar activity is in the low nanomolar range and 27,800-fold greater than that of natCu-NOTA-TP at 24 h post treatment. These results suggest that this combination of a cytotoxic TP agent with 64Cu has considerable potential for cancer treatment and PET imaging.
International Journal of Nanomedicine, 2016
The potential of gold nanoparticles (GNPs) as radiosensitizers for the treatment of malignant tum... more The potential of gold nanoparticles (GNPs) as radiosensitizers for the treatment of malignant tumors has been limited by the large quantities of GNPs that must be administered and the requirement for low-energy X-ray irradiation to optimize radiosensitization. In this study, we enhance the radiosensitivity of HCT116 human colorectal cells with tiopronin-coated GNPs (Tio-GNPs) combined with a low-energy X-ray (26 keV effective energy) source, similar to the Papillon 50 clinical irradiator used for topical irradiation of rectal tumors. Sensitizer enhancement ratios of 1.48 and 1.69 were measured in vitro, when the HCT116 cells were incubated with 0.1 mg/mL and 0.25 mg/mL of Tio-GNPs, respectively. In nude mice bearing the HCT116 tumor, intra-tumoral (IT) injection of Tio-GNPs allowed a 94 times higher quantity of Tio-GNPs to accumulate than was possible by intravenous injection and facilitated a significant tumor response. The time following irradiation, for tumors growing to four times their initial tumor volume (4Td) was 54 days for the IT injection of 366.3 µg of Tio-GNPs plus 10 Gy, compared to 37 days with radiation alone (P=0.0018). Conversely, no significant improvement was obtained when GNPs were injected intravenously before tumor irradiation (P=0.6547). In conclusion, IT injection of Tio-GNPs combined with low-energy X-rays can significantly reduce the growth of colorectal tumors.
Synthesis of Gly-ψ[(Z)CF═CH]-Phe, a Fluoroalkene Dipeptide Isostere, and Its Incorporation into a Leu-enkephalin Peptidomimetic
ACS Chemical Neuroscience, 2017
A new Leu-enkephalin peptidomimetic designed to explore the hydrogen bond acceptor ability of the... more A new Leu-enkephalin peptidomimetic designed to explore the hydrogen bond acceptor ability of the third peptide bond has been prepared and studied. This new analog is produced by replacing the third amide of Leu-enkephalin with a fluoroalkene. An efficient and innovative synthesis of the corresponding dipeptide surrogate Fmoc-Gly-ψ[(Z)CF═CH]-Phe-OH is described. The key step involves the alkylation of a tin dienolate from the less hindered face of its chiral sulfonamide auxiliary derived from camphor. Once its synthesis was complete, its incorporation into the peptidomimetic sequence was achieved on a solid support with chlorotrityl resin following the Fmoc strategy. The peptidomimetic was characterized using competition binding with [125I]-deltorphin I on membrane extracts of HEK293 cells expressing the mouse delta opioid receptor (DOPr) and based on its abilities to inhibit the electrically induced contractions of the mouse vas deferens and to activate the ERK1/2 signaling pathway in DRGF11/DOPr-GFP cells. Together with our previous observations, our findings strongly suggest that the third amide bond of Leu-enkephalin primarily acts as a hydrogen bond acceptor in DOPr. Consequently, this amide bond can be successfully replaced by an ester, a thioamide, or a fluoroalkene without greatly impacting the binding or biological activity of the corresponding analogs. The lipophilicity (LogD7.4) of the active analog was also measured. It appears that fluoroalkenes are almost as efficient at increasing the lipophilicity as normal alkenes.
64Cu-(DOTA)BVD15/BBN(6-14) as a novel dual-action peptide for breast cancer imaging
Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2009
Radiolabelled peptide heterodimer to improve breast and prostate cancer diagnosis by positron emission tomography
Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2008
Development of an Amyloid (AIAPP) Radiotracer for the Diagnosis and Management of Type 2 Diabetes Mellitus
Canadian Journal of Diabetes, 2015
Improved tumor targeting of F-18 bombesin analogs labeled by click chemistry is achieved by addition of a PEG side chain
64Cu-(DOTA) Lys4-BVD-15 as a novel agent for breast cancer imaging
Pure and Applied Chemistry, 1996
The radical reductions and allylations of a series of a-halo-P-alkoxy esters under bidentate chel... more The radical reductions and allylations of a series of a-halo-P-alkoxy esters under bidentate chelation-controlled conditions are reported and compared with the analogous reactions under non-chelating conditions. The addition of Lewis acids is shown to give excellent selectivity for the syn products in the case of reduction, and the anti products in the case of allylation. In some cases, ratios greater than 1OO:l are obtained. The reactions require initiation with EbB and can be inhibited by mand p-dinitrobenzene, which imply a radical-based mechanism. Iodides, bromides and phenyl selenides are all suitable substrates. Investigations also provide a rationale for the large excess of MgBr2.OEt2 which is apparently required in these reactions. Competition experiments provide a more detailed explanation of substrate reactivity.
Organic Letters, 2001
B. Determination of Relative Configuration C. NMR Spectra for Compounds 1, 7, 15, 17, 2a-b, 3a, 1... more B. Determination of Relative Configuration C. NMR Spectra for Compounds 1, 7, 15, 17, 2a-b, 3a, 14b, 18a-b, 20a-b, 22a-b and X-ray structure of 27b derivatized from pyrrolenine 22b. The preparation and characterization of alcohols 23a-c, 1 23d, 2 and 23e 3 have been reported previously. General procedures were used for the preparation of compounds 24a, 24c-e from corresponding alcohols 23a, 23c-e. To a solution of the appropriate alcohol (1 equiv) in CH 2 Cl 2 (0.2 M) at 0° C were added successively CBr 4 (1.1 equiv) and triphenylphosphine (1.1 equiv). The reaction mixture was brought to room temperature and stirred until the transformation of the alcohol was complete (2-3 hours), as indicated by thin-layer chromotography. The CH 2 Cl 2 was then evaporated, and a hexane:Et 2 O solution (1:1, 0.1 M) was added. The mixture was filtered through Celite and concentrated under reduced pressure. After purification by flash chromotography on silica gel (hexane:EtOAc, 19:1), bromide 24a was obtained as a colorless oil (90% from alcohol 23a). R ƒ 0.44 (hexane:EtOAc, 9:1); 1 H NMR (400 MHz, CDCl 3 ) δ 1.28 (t, J HO CO 2 Et Me N H CO 2 Et Me R N C O 2 Et Me R S Bth N S Bth = Conditions: (a) P(Ph) 3 , CBr 4 , CH 2 Cl 2, , 0°C. (b) RNH 2 , iPr 2 NEt, DMF. (c) BthSCl, Et 3 N, Et 2 O, 0°C.
![Research paper thumbnail of Radiosynthesis and bioconjugation of [18F]FPy5yne, a prosthetic group for the18F labeling of bioactive peptides](https://attachments.academia-assets.com/123108109/thumbnails/1.jpg)
](Journal of Labelled Compounds and Radiopharmaceuticals, 2008
A new 18 F-based prosthetic group has been prepared for the labeling of azide-modified peptides f... more A new 18 F-based prosthetic group has been prepared for the labeling of azide-modified peptides for use in PET imaging. 2-[ 18 F]fluoro-3-(hex-5-ynyloxy)pyridine ([ 18 F]FPy5yne, [ 18 F]-1) was prepared via efficient nucleophilic heteroaromatic substitution of either the corresponding 2-nitro (2) or 2-trimethylammonium trifluoromethanesulfonate pyridine (3). Best radiochemical yield of [ 18 F]FPy5yne from 2 was 91% by radioTLC (15 min, 1101C, DMSO). From 3, best radiochemical yield by radioTLC was 93% (15 min, 1101C, MeCN). HPLC-purified [ 18 F]FPy5yne was ligated to model peptide N 3 -(CH 2 ) 4 -CO-YK-RI-OH by way of Cu I -mediated Huisgen [3+2] cycloaddition in the presence of copper-stabilizing ligand tris(benzyltriazolylmethyl)amine (TBTA) and N,N-diisopropylethylamine (DIEA). Bioconjugate radiochemical yields were obtained in average yields of 89%78.6% (n = 4), as judged by radioHPLC. Best non-decay-corrected, collected radiochemical yield of modified peptide from end-of-bombardment was 5.8% (18.7% decay-corrected), with a total preparation time of 160 min from start of synthesis.
Chemical Physics Letters, 1989
We report the preparation and crystal structure of 3-methyl-4-methoxy-4'-nitrostilbene (MMONS). M... more We report the preparation and crystal structure of 3-methyl-4-methoxy-4'-nitrostilbene (MMONS). MMONS generates second-harmonic radiation with a powder efficiency 1250 times that of urea; this is the largest measured powder SHG efficiency reported to date. MMONS crystallizes in the space group Aba2; the packing is made up of stacks of four molecules in a donoracceptor-acceptor-donor configuration with n-n interactions resulting in short intermolecular distances between these four phenyl rings of 3.36-3.50 A. We suggest that charge-transfer excitons within the crystal may account for the large observed nonlinearity.
Chemical Communications, 1997
Peptidic receptors bearing a crown ether side chain show enantioselective recognition of aromatic... more Peptidic receptors bearing a crown ether side chain show enantioselective recognition of aromatic carboxylate and ammonium species and could be useful in chiral separation technology.
Radiolabeled BODIPYs: An overview
Porphyrin Science by Women, 2021
Pd‐Catalyzed Sonogashira Cross‐Coupling Reactions of gem ‐Dibromovinyl BODIPY Derivatives
European Journal of Organic Chemistry, 2021
CCDC 2008305: Experimental Crystal Structure Determination
Bifunctional chelates for 64Cu radiolabelling of BBN peptides for PET imaging, a comparative study
The Journal of Nuclear Medicine, 2011
Theranostic potential of a new [64Cu]-radiolabeled R-954 conjugate for kinin B1R positive tumors
The Journal of Nuclear Medicine, 2016
Peptide Science, 2018
Enkephalins are pentapeptidic endogenous ligands that regulate nociception by binding to mu (MOP)... more Enkephalins are pentapeptidic endogenous ligands that regulate nociception by binding to mu (MOP) and delta (DOP) opioid receptors. To further explore the role of the leucine residue of Leu‐enkephalin, 12 peptidomimetic analogs were synthesized by systematically replacing this residue with non‐natural amino acids. The analogs were tested for their ability to bind DOP and MOP. We also investigated the potency of these analogs to inhibit cAMP production and to recruit β‐arrestin 2 via both receptors. We found that replacement of the leucine residue by substituted non‐natural amino acid derivatives of alanine, cycloleucine, or isoleucine was generally well tolerated. By contrast, substituting leucine with homoproline greatly reduced the affinity for DOP and, to a lesser extent, for MOP. Interestingly, when compared to Leu‐enkephalin, analogs containing either aza‐β‐homoleucine or cycloleucine showed a bias toward inhibition of cAMP production through the activation of DOP but not MOP. ...
High Cytotoxic Effect by Combining Copper-64 with a NOTA–Terpyridine Platinum Conjugate
Journal of Medicinal Chemistry, 2021
Terpyridine platinum (TP)-based chemotherapeutic agents target three-dimensional structures on DN... more Terpyridine platinum (TP)-based chemotherapeutic agents target three-dimensional structures on DNA known as G-quadruplexes. We report the rational design and synthesis of a TP conjugate combined with copper-64 (64Cu), the decay characteristics of which include emission of β- and Auger electrons for radiotherapy and β+ particles for positron emission tomography (PET) imaging. The present experimental studies show that the novel [64Cu]Cu-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-TP is stable, permitting selective killing of cancer cells. The antitumor activity of [64Cu]Cu-NOTA-TP at high apparent molar activity is in the low nanomolar range and 27,800-fold greater than that of natCu-NOTA-TP at 24 h post treatment. These results suggest that this combination of a cytotoxic TP agent with 64Cu has considerable potential for cancer treatment and PET imaging.
International Journal of Nanomedicine, 2016
The potential of gold nanoparticles (GNPs) as radiosensitizers for the treatment of malignant tum... more The potential of gold nanoparticles (GNPs) as radiosensitizers for the treatment of malignant tumors has been limited by the large quantities of GNPs that must be administered and the requirement for low-energy X-ray irradiation to optimize radiosensitization. In this study, we enhance the radiosensitivity of HCT116 human colorectal cells with tiopronin-coated GNPs (Tio-GNPs) combined with a low-energy X-ray (26 keV effective energy) source, similar to the Papillon 50 clinical irradiator used for topical irradiation of rectal tumors. Sensitizer enhancement ratios of 1.48 and 1.69 were measured in vitro, when the HCT116 cells were incubated with 0.1 mg/mL and 0.25 mg/mL of Tio-GNPs, respectively. In nude mice bearing the HCT116 tumor, intra-tumoral (IT) injection of Tio-GNPs allowed a 94 times higher quantity of Tio-GNPs to accumulate than was possible by intravenous injection and facilitated a significant tumor response. The time following irradiation, for tumors growing to four times their initial tumor volume (4Td) was 54 days for the IT injection of 366.3 µg of Tio-GNPs plus 10 Gy, compared to 37 days with radiation alone (P=0.0018). Conversely, no significant improvement was obtained when GNPs were injected intravenously before tumor irradiation (P=0.6547). In conclusion, IT injection of Tio-GNPs combined with low-energy X-rays can significantly reduce the growth of colorectal tumors.
Synthesis of Gly-ψ[(Z)CF═CH]-Phe, a Fluoroalkene Dipeptide Isostere, and Its Incorporation into a Leu-enkephalin Peptidomimetic
ACS Chemical Neuroscience, 2017
A new Leu-enkephalin peptidomimetic designed to explore the hydrogen bond acceptor ability of the... more A new Leu-enkephalin peptidomimetic designed to explore the hydrogen bond acceptor ability of the third peptide bond has been prepared and studied. This new analog is produced by replacing the third amide of Leu-enkephalin with a fluoroalkene. An efficient and innovative synthesis of the corresponding dipeptide surrogate Fmoc-Gly-ψ[(Z)CF═CH]-Phe-OH is described. The key step involves the alkylation of a tin dienolate from the less hindered face of its chiral sulfonamide auxiliary derived from camphor. Once its synthesis was complete, its incorporation into the peptidomimetic sequence was achieved on a solid support with chlorotrityl resin following the Fmoc strategy. The peptidomimetic was characterized using competition binding with [125I]-deltorphin I on membrane extracts of HEK293 cells expressing the mouse delta opioid receptor (DOPr) and based on its abilities to inhibit the electrically induced contractions of the mouse vas deferens and to activate the ERK1/2 signaling pathway in DRGF11/DOPr-GFP cells. Together with our previous observations, our findings strongly suggest that the third amide bond of Leu-enkephalin primarily acts as a hydrogen bond acceptor in DOPr. Consequently, this amide bond can be successfully replaced by an ester, a thioamide, or a fluoroalkene without greatly impacting the binding or biological activity of the corresponding analogs. The lipophilicity (LogD7.4) of the active analog was also measured. It appears that fluoroalkenes are almost as efficient at increasing the lipophilicity as normal alkenes.
64Cu-(DOTA)BVD15/BBN(6-14) as a novel dual-action peptide for breast cancer imaging
Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2009
Radiolabelled peptide heterodimer to improve breast and prostate cancer diagnosis by positron emission tomography
Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2008
Development of an Amyloid (AIAPP) Radiotracer for the Diagnosis and Management of Type 2 Diabetes Mellitus
Canadian Journal of Diabetes, 2015
Improved tumor targeting of F-18 bombesin analogs labeled by click chemistry is achieved by addition of a PEG side chain
64Cu-(DOTA) Lys4-BVD-15 as a novel agent for breast cancer imaging
Pure and Applied Chemistry, 1996
The radical reductions and allylations of a series of a-halo-P-alkoxy esters under bidentate chel... more The radical reductions and allylations of a series of a-halo-P-alkoxy esters under bidentate chelation-controlled conditions are reported and compared with the analogous reactions under non-chelating conditions. The addition of Lewis acids is shown to give excellent selectivity for the syn products in the case of reduction, and the anti products in the case of allylation. In some cases, ratios greater than 1OO:l are obtained. The reactions require initiation with EbB and can be inhibited by mand p-dinitrobenzene, which imply a radical-based mechanism. Iodides, bromides and phenyl selenides are all suitable substrates. Investigations also provide a rationale for the large excess of MgBr2.OEt2 which is apparently required in these reactions. Competition experiments provide a more detailed explanation of substrate reactivity.
Organic Letters, 2001
B. Determination of Relative Configuration C. NMR Spectra for Compounds 1, 7, 15, 17, 2a-b, 3a, 1... more B. Determination of Relative Configuration C. NMR Spectra for Compounds 1, 7, 15, 17, 2a-b, 3a, 14b, 18a-b, 20a-b, 22a-b and X-ray structure of 27b derivatized from pyrrolenine 22b. The preparation and characterization of alcohols 23a-c, 1 23d, 2 and 23e 3 have been reported previously. General procedures were used for the preparation of compounds 24a, 24c-e from corresponding alcohols 23a, 23c-e. To a solution of the appropriate alcohol (1 equiv) in CH 2 Cl 2 (0.2 M) at 0° C were added successively CBr 4 (1.1 equiv) and triphenylphosphine (1.1 equiv). The reaction mixture was brought to room temperature and stirred until the transformation of the alcohol was complete (2-3 hours), as indicated by thin-layer chromotography. The CH 2 Cl 2 was then evaporated, and a hexane:Et 2 O solution (1:1, 0.1 M) was added. The mixture was filtered through Celite and concentrated under reduced pressure. After purification by flash chromotography on silica gel (hexane:EtOAc, 19:1), bromide 24a was obtained as a colorless oil (90% from alcohol 23a). R ƒ 0.44 (hexane:EtOAc, 9:1); 1 H NMR (400 MHz, CDCl 3 ) δ 1.28 (t, J HO CO 2 Et Me N H CO 2 Et Me R N C O 2 Et Me R S Bth N S Bth = Conditions: (a) P(Ph) 3 , CBr 4 , CH 2 Cl 2, , 0°C. (b) RNH 2 , iPr 2 NEt, DMF. (c) BthSCl, Et 3 N, Et 2 O, 0°C.
Journal of Labelled Compounds and Radiopharmaceuticals, 2008
A new 18 F-based prosthetic group has been prepared for the labeling of azide-modified peptides f... more A new 18 F-based prosthetic group has been prepared for the labeling of azide-modified peptides for use in PET imaging. 2-[ 18 F]fluoro-3-(hex-5-ynyloxy)pyridine ([ 18 F]FPy5yne, [ 18 F]-1) was prepared via efficient nucleophilic heteroaromatic substitution of either the corresponding 2-nitro (2) or 2-trimethylammonium trifluoromethanesulfonate pyridine (3). Best radiochemical yield of [ 18 F]FPy5yne from 2 was 91% by radioTLC (15 min, 1101C, DMSO). From 3, best radiochemical yield by radioTLC was 93% (15 min, 1101C, MeCN). HPLC-purified [ 18 F]FPy5yne was ligated to model peptide N 3 -(CH 2 ) 4 -CO-YK-RI-OH by way of Cu I -mediated Huisgen [3+2] cycloaddition in the presence of copper-stabilizing ligand tris(benzyltriazolylmethyl)amine (TBTA) and N,N-diisopropylethylamine (DIEA). Bioconjugate radiochemical yields were obtained in average yields of 89%78.6% (n = 4), as judged by radioHPLC. Best non-decay-corrected, collected radiochemical yield of modified peptide from end-of-bombardment was 5.8% (18.7% decay-corrected), with a total preparation time of 160 min from start of synthesis.
Chemical Physics Letters, 1989
We report the preparation and crystal structure of 3-methyl-4-methoxy-4'-nitrostilbene (MMONS). M... more We report the preparation and crystal structure of 3-methyl-4-methoxy-4'-nitrostilbene (MMONS). MMONS generates second-harmonic radiation with a powder efficiency 1250 times that of urea; this is the largest measured powder SHG efficiency reported to date. MMONS crystallizes in the space group Aba2; the packing is made up of stacks of four molecules in a donoracceptor-acceptor-donor configuration with n-n interactions resulting in short intermolecular distances between these four phenyl rings of 3.36-3.50 A. We suggest that charge-transfer excitons within the crystal may account for the large observed nonlinearity.
Chemical Communications, 1997
Peptidic receptors bearing a crown ether side chain show enantioselective recognition of aromatic... more Peptidic receptors bearing a crown ether side chain show enantioselective recognition of aromatic carboxylate and ammonium species and could be useful in chiral separation technology.