Yves Lelievre - Academia.edu (original) (raw)

Papers by Yves Lelievre

Research paper thumbnail of Of Antibiotics an Inhibitor of Mammaliancollagenase Active at Micromolar Concentrations from an Actinomycete Culture Broth

Anti-collagenase activity was detected in the culture supernatant of an Actinomycete strain S 437... more Anti-collagenase activity was detected in the culture supernatant of an Actinomycete strain S 4373. The molecule was purified by solvent extraction, mediumpressure and high pressure reverse phase chromatography and finally by HPLCgel filtration. The pure product was analyzed by mass spectroscopy and was identified as actinonin, a knownpseudopeptide antibiotic. The Ki was determined as 1.4 im and this value was confirmed using pure synthetic actinonin. 1757

Research paper thumbnail of Elaboration de vecteurs d'ADN, substrats de gélatinases

Research paper thumbnail of Synthesis and Purification of Active Human Tissue Plasminogen Activator From Escherichia coli

Research paper thumbnail of From Random Screening of Chemical Libraries to the Optimization of FPP-Competitive Inhibitors of Farnesyltransferase

Farnesyltransferase Inhibitors in Cancer Therapy, 2000

Research paper thumbnail of Betulinic Acid Derivatives:  A New Class of Human Immunodeficiency Virus Type 1 Specific Inhibitors with a New Mode of Action

Journal of Medicinal Chemistry, 1996

A series of omega-undecanoic amides of lup-20(29)-en-28-oic acid derivatives were synthesized and... more A series of omega-undecanoic amides of lup-20(29)-en-28-oic acid derivatives were synthesized and evaluated for activity in CEM 4 and MT-4 cell cultures against human immunodeficiency virus type 1 (HIV-1) strain IIIB/LAI. The potent HIV inhibitors which emerged, compounds 5a, 16a, and 17b, were all derivatives of betulinic acid (3beta-hydroxylup-20(29)-en-28-oic acid). No activity was found against HIV-2 strain ROD. Compound 5a showed no inhibition of HIV-1 reverse transcriptase activity with poly(C).oligo(dG) as template/primer, nor did it inhibit HIV-1 protease. Additional mechanistic studies revealed that this class of compounds interfere with HIV-1 entry in the cells at a postbinding step.

Research paper thumbnail of Novel Conformationally Extended Naphthalene-Based Inhibitors of Farnesyltransferase

Journal of Medicinal Chemistry, 1997

Research paper thumbnail of Anti-HIV activity of N-(2,3-dihalogenopropyl)- and N-allyl-glycine containing pentapeptides

Bioorganic & Medicinal Chemistry Letters, 1994

A series of peptides containing N-(2,3-dihalopropyl)-glycine or alanine residues has been prepare... more A series of peptides containing N-(2,3-dihalopropyl)-glycine or alanine residues has been prepared as potential suicide substrates of the HIV pol-protease or as enzyme-activated prodrugs. Halogenation of unsaturated N-ally1 peptide precursors in dichloromethane occurs with participation of a neighboring amide group and leads to halohydrins instead of the expected dihalides. Use of X2/ Lii HOAc conditions gives the desired dihalogenated derivatives. These functionalized substrate analogs are not inhibitors of the enzyme. However, Boc-A1a-Phe-N-(2,3-dhalogenopropyl)-Gly-Ile-Val-OMe (halogen= Br and Cl) inhibit the cytopathic effect induced by HIV-l in CEM cell cultures and the reverse transcriptase activity in cell culture supematants. The corresponding unsaturated N-ally1 precursor also displays an antiviral effect.

Research paper thumbnail of Peptoid mimics of a C2-symmetric inhibitor of the HIV-1 protease

Bioorganic & Medicinal Chemistry Letters, 1994

... 1994 Elsevier Science Ltd Printed in Great Britain AB rights reserved 0960894X 94 7 00+0 00 0... more ... 1994 Elsevier Science Ltd Printed in Great Britain AB rights reserved 0960894X 94 7 00+0 00 0960894X(94)001405 PEPTOID MIMICS OF A QSYMMETRIC INHIBITOR OF THE HIV1 PROTEASE. JeanPaul Mazaleyrat*, Isabelle Rage, Abdel Maiek Mouna, Jaroslav Savrda and ...

Research paper thumbnail of Local constrained shifty pseudopeptides inhibitors of rasfarnesyl transferase

Bioorganic & Medicinal Chemistry Letters, 1995

Pseudopeptide analogues related to the C-terminal tetrapeptide of ras-protein (Cys-Val-X-Met) wer... more Pseudopeptide analogues related to the C-terminal tetrapeptide of ras-protein (Cys-Val-X-Met) were synthesized and evaluated for inhibition of ras farnesyl transferase (FTase). We demonstrate that the introduction of a shifty amino acid related to Cys instead of Cys-Val and a tetrahydroisoquinoline carboxylic acid (TIC) instead of Phe lead to potent inhibitors of FTase on isolated enzyme or on cell based tests.

Research paper thumbnail of Constrained analogs of KCVFM with improved inhibitory properties against farnesyl transferase

Bioorganic & Medicinal Chemistry Letters, 1995

... François-Frédéric Clerc * , Jean-Dominique Guitton * , Nadine Fromage , Yves Lelièvre , Marc ... more ... François-Frédéric Clerc * , Jean-Dominique Guitton * , Nadine Fromage , Yves Lelièvre , Marc Duchesne , Bruno Tocqué , Evelyne James-Surcouf , Alain ... conformation for the CA1A2M type peptides11.13 and in agreement with the proposition made by Hamilton, Sebti and ...

Research paper thumbnail of Synthesis and conformational analysis of peptide inhibitors of farnesyltransferase

Bioorganic & Medicinal Chemistry, 1997

Farnesylation of the ras oncogene product by Farnesyl Transferase (FTase) is known to be a critic... more Farnesylation of the ras oncogene product by Farnesyl Transferase (FTase) is known to be a critical step in cell transformation leading to uncontrolled proliferation. The peptide CysValTicMet is a potent FTase inhibitor, but its degradation by amino-peptidases and its only weak internalization into cells make it a bad candidate for a future cancer drug. We have prepared improved CysValTicMet analogues using several approaches: (i) amino terminal modifications or introduction of pseudopeptides or non-natural amino acids to increase proteolytic stability, (ii) introduction of hydrophobic aliphatic chains to increase cell internalization and metabolic stability and (iii) transformation into prodrugs. Additionally, we have carried out comparative conformational analysis studies by molecular dynamics of some of the here presented peptides and of our recently described peptidomimetic inhibitors of FTase.

Research paper thumbnail of Inhibition of cathepsin D by tripeptides containing statine analogs

Biochemical Pharmacology, 1999

Various analogs of statine, a remarkable amino acid component of the protease inhibitor pepstatin... more Various analogs of statine, a remarkable amino acid component of the protease inhibitor pepstatine, were synthesized and evaluated as tripeptide derivatives for their activity against cathepsin D and HIV-1 protease.

Research paper thumbnail of RPR113228, a Novel Farnesyl Protein Transferase Inhibitor Produced by Chrysosporium lobatum

The Journal of Antibiotics, 1995

Research paper thumbnail of Of Antibiotics an Inhibitor of Mammaliancollagenase Active at Micromolar Concentrations from an Actinomycete Culture Broth

Anti-collagenase activity was detected in the culture supernatant of an Actinomycete strain S 437... more Anti-collagenase activity was detected in the culture supernatant of an Actinomycete strain S 4373. The molecule was purified by solvent extraction, mediumpressure and high pressure reverse phase chromatography and finally by HPLCgel filtration. The pure product was analyzed by mass spectroscopy and was identified as actinonin, a knownpseudopeptide antibiotic. The Ki was determined as 1.4 im and this value was confirmed using pure synthetic actinonin. 1757

Research paper thumbnail of Elaboration de vecteurs d'ADN, substrats de gélatinases

Research paper thumbnail of Synthesis and Purification of Active Human Tissue Plasminogen Activator From Escherichia coli

Research paper thumbnail of From Random Screening of Chemical Libraries to the Optimization of FPP-Competitive Inhibitors of Farnesyltransferase

Farnesyltransferase Inhibitors in Cancer Therapy, 2000

Research paper thumbnail of Betulinic Acid Derivatives:  A New Class of Human Immunodeficiency Virus Type 1 Specific Inhibitors with a New Mode of Action

Journal of Medicinal Chemistry, 1996

A series of omega-undecanoic amides of lup-20(29)-en-28-oic acid derivatives were synthesized and... more A series of omega-undecanoic amides of lup-20(29)-en-28-oic acid derivatives were synthesized and evaluated for activity in CEM 4 and MT-4 cell cultures against human immunodeficiency virus type 1 (HIV-1) strain IIIB/LAI. The potent HIV inhibitors which emerged, compounds 5a, 16a, and 17b, were all derivatives of betulinic acid (3beta-hydroxylup-20(29)-en-28-oic acid). No activity was found against HIV-2 strain ROD. Compound 5a showed no inhibition of HIV-1 reverse transcriptase activity with poly(C).oligo(dG) as template/primer, nor did it inhibit HIV-1 protease. Additional mechanistic studies revealed that this class of compounds interfere with HIV-1 entry in the cells at a postbinding step.

Research paper thumbnail of Novel Conformationally Extended Naphthalene-Based Inhibitors of Farnesyltransferase

Journal of Medicinal Chemistry, 1997

Research paper thumbnail of Anti-HIV activity of N-(2,3-dihalogenopropyl)- and N-allyl-glycine containing pentapeptides

Bioorganic & Medicinal Chemistry Letters, 1994

A series of peptides containing N-(2,3-dihalopropyl)-glycine or alanine residues has been prepare... more A series of peptides containing N-(2,3-dihalopropyl)-glycine or alanine residues has been prepared as potential suicide substrates of the HIV pol-protease or as enzyme-activated prodrugs. Halogenation of unsaturated N-ally1 peptide precursors in dichloromethane occurs with participation of a neighboring amide group and leads to halohydrins instead of the expected dihalides. Use of X2/ Lii HOAc conditions gives the desired dihalogenated derivatives. These functionalized substrate analogs are not inhibitors of the enzyme. However, Boc-A1a-Phe-N-(2,3-dhalogenopropyl)-Gly-Ile-Val-OMe (halogen= Br and Cl) inhibit the cytopathic effect induced by HIV-l in CEM cell cultures and the reverse transcriptase activity in cell culture supematants. The corresponding unsaturated N-ally1 precursor also displays an antiviral effect.

Research paper thumbnail of Peptoid mimics of a C2-symmetric inhibitor of the HIV-1 protease

Bioorganic & Medicinal Chemistry Letters, 1994

... 1994 Elsevier Science Ltd Printed in Great Britain AB rights reserved 0960894X 94 7 00+0 00 0... more ... 1994 Elsevier Science Ltd Printed in Great Britain AB rights reserved 0960894X 94 7 00+0 00 0960894X(94)001405 PEPTOID MIMICS OF A QSYMMETRIC INHIBITOR OF THE HIV1 PROTEASE. JeanPaul Mazaleyrat*, Isabelle Rage, Abdel Maiek Mouna, Jaroslav Savrda and ...

Research paper thumbnail of Local constrained shifty pseudopeptides inhibitors of rasfarnesyl transferase

Bioorganic & Medicinal Chemistry Letters, 1995

Pseudopeptide analogues related to the C-terminal tetrapeptide of ras-protein (Cys-Val-X-Met) wer... more Pseudopeptide analogues related to the C-terminal tetrapeptide of ras-protein (Cys-Val-X-Met) were synthesized and evaluated for inhibition of ras farnesyl transferase (FTase). We demonstrate that the introduction of a shifty amino acid related to Cys instead of Cys-Val and a tetrahydroisoquinoline carboxylic acid (TIC) instead of Phe lead to potent inhibitors of FTase on isolated enzyme or on cell based tests.

Research paper thumbnail of Constrained analogs of KCVFM with improved inhibitory properties against farnesyl transferase

Bioorganic & Medicinal Chemistry Letters, 1995

... François-Frédéric Clerc * , Jean-Dominique Guitton * , Nadine Fromage , Yves Lelièvre , Marc ... more ... François-Frédéric Clerc * , Jean-Dominique Guitton * , Nadine Fromage , Yves Lelièvre , Marc Duchesne , Bruno Tocqué , Evelyne James-Surcouf , Alain ... conformation for the CA1A2M type peptides11.13 and in agreement with the proposition made by Hamilton, Sebti and ...

Research paper thumbnail of Synthesis and conformational analysis of peptide inhibitors of farnesyltransferase

Bioorganic & Medicinal Chemistry, 1997

Farnesylation of the ras oncogene product by Farnesyl Transferase (FTase) is known to be a critic... more Farnesylation of the ras oncogene product by Farnesyl Transferase (FTase) is known to be a critical step in cell transformation leading to uncontrolled proliferation. The peptide CysValTicMet is a potent FTase inhibitor, but its degradation by amino-peptidases and its only weak internalization into cells make it a bad candidate for a future cancer drug. We have prepared improved CysValTicMet analogues using several approaches: (i) amino terminal modifications or introduction of pseudopeptides or non-natural amino acids to increase proteolytic stability, (ii) introduction of hydrophobic aliphatic chains to increase cell internalization and metabolic stability and (iii) transformation into prodrugs. Additionally, we have carried out comparative conformational analysis studies by molecular dynamics of some of the here presented peptides and of our recently described peptidomimetic inhibitors of FTase.

Research paper thumbnail of Inhibition of cathepsin D by tripeptides containing statine analogs

Biochemical Pharmacology, 1999

Various analogs of statine, a remarkable amino acid component of the protease inhibitor pepstatin... more Various analogs of statine, a remarkable amino acid component of the protease inhibitor pepstatine, were synthesized and evaluated as tripeptide derivatives for their activity against cathepsin D and HIV-1 protease.

Research paper thumbnail of RPR113228, a Novel Farnesyl Protein Transferase Inhibitor Produced by Chrysosporium lobatum

The Journal of Antibiotics, 1995