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Terrence R Burke - One of the best experts on this subject based on the ideXlab platform.
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design and synthesis of fmoc thr po oh opom for the preparation of peptide prodrugs containing Phosphothreonine in fully protected form
Chemistry & Biodiversity, 2014Co-Authors: Wenjian Qian, Christopher C Lai, James A Kelley, Terrence R BurkeAbstract:The design and efficient synthesis of N-Fmoc-Phosphothreonine protected by a mono-(pivaloyloxy)methyl (POM) moiety at its phosphoryl group (Fmoc-Thr[PO(OH)(OPOM)]-OH, 1, is reported. This reagent is suitable for solid-phase syntheses employing acid-labile resins and Fmoc-based protocols. It allows the preparation of Phosphothreonine (pThr)-containing peptides bearing bis-POM-phosphoryl protection. The methodology allows the first reported synthesis of pThr-containing polypeptides having bioreversible prodrug protection, and as such it should be useful in a variety of biological applications.
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peptide based inhibitors of plk1 polo box domain containing mono anionic Phosphothreonine esters and their pivaloyloxymethyl prodrugs
Chemistry & Biology, 2013Co-Authors: Wenjian Qian, Michael B Yaffe, Jungeun Park, Daniel Lim, Sukyoul Park, Ki Won Lee, Kyung S Lee, Terrence R BurkeAbstract:(Chemistry & Biology 20, 1255–1264, October 24, 2013)This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).This article has been retracted at the request of the authors.Our paper reported small peptide inhibitors of the Plk1 polo-box domain (PBD) that were designed to contain monoanionic Phosphothreonine esters. Subsequent analysis has revealed that the structures of peptides 2b–2n, 2c∗, 2m∗, and 3; their associated serine to alanine (S/A) variants; and the X-ray cocrystal structure of 2m bound to the Plk1 PBD (PDB accession code 4MLU) are not as presented in the paper. The pThr residues, which were reported as being monoanionic or neutral, are instead dianionic and monoanionic, respectively. Therefore, the interpretation of the data as reflecting the ability of peptides containing a monoanionic Phosphothreonine residue to exhibit high PBD-binding affinity and enhanced cellular efficacy as well as the role of pivaloyloxymethyl (POM) prodrug protection in the observed biological effects are not valid in light of the incorrect structural assignments. As a result, the authors retract the paper.
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design and synthesis of a reagent for solid phase incorporation of the Phosphothreonine mimetic 2s 3r 2 amino 3 methyl 4 phosphonobutyric acid pmab into peptides in a bio reversible phosphonyl bis pivaloyloxymethyl pom prodrug form
Amino Acids, 2013Co-Authors: Wenjian Qian, Terrence R BurkeAbstract:Reported herein are the synthesis and solid-phase peptide incorporation of N-Fmoc-(2S,3R)-2-amino-3-methyl-4-phosphonobutyric acid bis-pivaloyloxymethyl phosphoryl ester [Fmoc-Pmab(POM)2-OH, 2] as a phosphatase-stable Phosphothreonine (pThr) mimetic bearing orthogonal protection suitable for the synthesis of Pmab-containing peptides having bio-reversible protection of the phosphonic acid moiety. This represents the first report of a bio-reversibly protected pThr mimetic in a form suitable for facile solid-phase peptide synthesis.
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investigation of unanticipated alkylation at the n π position of a histidyl residue under mitsunobu conditions and synthesis of orthogonally protected histidine analogues
Journal of Organic Chemistry, 2011Co-Authors: Wenjian Qian, Fa Liu, Terrence R BurkeAbstract:We had previously reported that Mitsunobu-based introduction of alkyl substituents onto the imidazole N(π)-position of a key histidine residue in Phosphothreonine-containing peptides can impart high binding affinity against the polo-box domain of polo-like kinase 1. Our current paper investigates the mechanism leading to this N(π)-alkylation and provides synthetic methodologies that permit the facile synthesis of histidine N(π)-modified peptides. These agents represent new and potentially important tools for biological studies.
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preparation of orthogonally protected 2s 3r 2 amino 3 methyl 4 phosphonobutyric acid pmab as a phosphatase stable Phosphothreonine mimetic and its use in the synthesis of polo box domain binding peptides
Tetrahedron, 2009Co-Authors: Fa Liu, Jungeun Park, Kyung S Lee, Terrence R BurkeAbstract:Abstract Reported herein is the first stereoselective synthesis of (2S,3R)-4-[bis-(tert-butyloxy)phosphinyl]-2-[(9H-fluoren-9-ylmethoxy)carbonyl]amino-3-methylbutanoic acid [(N-Fmoc, O,O-(bis-(tert-butyl))-Pmab), 4] as a hydrolytically-stable Phosphothreonine mimetic bearing orthogonal protection compatible with standard solid-phase protocols. The synthetic approach used employs Evans' oxazolidinone for chiral induction. Also presented is the application of 4 in the solid-phase synthesis of polo-like kinase 1 (Plk1) polo box domain (PBD)-binding peptides. These Pmab-containing peptides retain PBD binding efficacy similar to a parent pThr containing peptide. Reagent 4 should be a highly useful reagent for the preparation of signal transduction-directed peptides.
Wenjian Qian - One of the best experts on this subject based on the ideXlab platform.
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design and synthesis of fmoc thr po oh opom for the preparation of peptide prodrugs containing Phosphothreonine in fully protected form
Chemistry & Biodiversity, 2014Co-Authors: Wenjian Qian, Christopher C Lai, James A Kelley, Terrence R BurkeAbstract:The design and efficient synthesis of N-Fmoc-Phosphothreonine protected by a mono-(pivaloyloxy)methyl (POM) moiety at its phosphoryl group (Fmoc-Thr[PO(OH)(OPOM)]-OH, 1, is reported. This reagent is suitable for solid-phase syntheses employing acid-labile resins and Fmoc-based protocols. It allows the preparation of Phosphothreonine (pThr)-containing peptides bearing bis-POM-phosphoryl protection. The methodology allows the first reported synthesis of pThr-containing polypeptides having bioreversible prodrug protection, and as such it should be useful in a variety of biological applications.
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peptide based inhibitors of plk1 polo box domain containing mono anionic Phosphothreonine esters and their pivaloyloxymethyl prodrugs
Chemistry & Biology, 2013Co-Authors: Wenjian Qian, Michael B Yaffe, Jungeun Park, Daniel Lim, Sukyoul Park, Ki Won Lee, Kyung S Lee, Terrence R BurkeAbstract:(Chemistry & Biology 20, 1255–1264, October 24, 2013)This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).This article has been retracted at the request of the authors.Our paper reported small peptide inhibitors of the Plk1 polo-box domain (PBD) that were designed to contain monoanionic Phosphothreonine esters. Subsequent analysis has revealed that the structures of peptides 2b–2n, 2c∗, 2m∗, and 3; their associated serine to alanine (S/A) variants; and the X-ray cocrystal structure of 2m bound to the Plk1 PBD (PDB accession code 4MLU) are not as presented in the paper. The pThr residues, which were reported as being monoanionic or neutral, are instead dianionic and monoanionic, respectively. Therefore, the interpretation of the data as reflecting the ability of peptides containing a monoanionic Phosphothreonine residue to exhibit high PBD-binding affinity and enhanced cellular efficacy as well as the role of pivaloyloxymethyl (POM) prodrug protection in the observed biological effects are not valid in light of the incorrect structural assignments. As a result, the authors retract the paper.
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design and synthesis of a reagent for solid phase incorporation of the Phosphothreonine mimetic 2s 3r 2 amino 3 methyl 4 phosphonobutyric acid pmab into peptides in a bio reversible phosphonyl bis pivaloyloxymethyl pom prodrug form
Amino Acids, 2013Co-Authors: Wenjian Qian, Terrence R BurkeAbstract:Reported herein are the synthesis and solid-phase peptide incorporation of N-Fmoc-(2S,3R)-2-amino-3-methyl-4-phosphonobutyric acid bis-pivaloyloxymethyl phosphoryl ester [Fmoc-Pmab(POM)2-OH, 2] as a phosphatase-stable Phosphothreonine (pThr) mimetic bearing orthogonal protection suitable for the synthesis of Pmab-containing peptides having bio-reversible protection of the phosphonic acid moiety. This represents the first report of a bio-reversibly protected pThr mimetic in a form suitable for facile solid-phase peptide synthesis.
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investigation of unanticipated alkylation at the n π position of a histidyl residue under mitsunobu conditions and synthesis of orthogonally protected histidine analogues
Journal of Organic Chemistry, 2011Co-Authors: Wenjian Qian, Fa Liu, Terrence R BurkeAbstract:We had previously reported that Mitsunobu-based introduction of alkyl substituents onto the imidazole N(π)-position of a key histidine residue in Phosphothreonine-containing peptides can impart high binding affinity against the polo-box domain of polo-like kinase 1. Our current paper investigates the mechanism leading to this N(π)-alkylation and provides synthetic methodologies that permit the facile synthesis of histidine N(π)-modified peptides. These agents represent new and potentially important tools for biological studies.
Juan J Guillin - One of the best experts on this subject based on the ideXlab platform.
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stereoselective synthesis of α monofluorinated phosphonate mimetics of naturally occurring phosphoserine and Phosphothreonine via electrophilic fluorination of lithiated bis lactim ethers
Chemical Communications, 2002Co-Authors: María José Ruiz, Vicente Ojea, Jose M Quintela, Juan J GuillinAbstract:Electrophilic fluorinations of lithiated bis-lactim ethers derived from cyclo-[L-AP4-D-Val] allow a direct access to α-monofluorinated phosphonate mimetics of naturally occurring phosphoserine and Phosphothreonine, in enantiomerically pure form and suitably protected for solid-phase peptide synthesis.
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stereoselective synthesis of alpha monofluorinated phosphonate mimetics of naturally occurring phosphoserine and Phosphothreonine via electrophilic fluorination of lithiated bis lactim ethers
Chemical Communications, 2002Co-Authors: María José Ruiz, Vicente Ojea, Jose M Quintela, Juan J GuillinAbstract:Electrophilic fluorinations of lithiated bis-lactim ethers derived from cyclo-[L-AP4-D-Val] allow a direct access to α-monofluorinated phosphonate mimetics of naturally occurring phosphoserine and Phosphothreonine, in enantiomerically pure form and suitably protected for solid-phase peptide synthesis.
María José Ruiz - One of the best experts on this subject based on the ideXlab platform.
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stereoselective synthesis of α monofluorinated phosphonate mimetics of naturally occurring phosphoserine and Phosphothreonine via electrophilic fluorination of lithiated bis lactim ethers
Chemical Communications, 2002Co-Authors: María José Ruiz, Vicente Ojea, Jose M Quintela, Juan J GuillinAbstract:Electrophilic fluorinations of lithiated bis-lactim ethers derived from cyclo-[L-AP4-D-Val] allow a direct access to α-monofluorinated phosphonate mimetics of naturally occurring phosphoserine and Phosphothreonine, in enantiomerically pure form and suitably protected for solid-phase peptide synthesis.
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stereoselective synthesis of alpha monofluorinated phosphonate mimetics of naturally occurring phosphoserine and Phosphothreonine via electrophilic fluorination of lithiated bis lactim ethers
Chemical Communications, 2002Co-Authors: María José Ruiz, Vicente Ojea, Jose M Quintela, Juan J GuillinAbstract:Electrophilic fluorinations of lithiated bis-lactim ethers derived from cyclo-[L-AP4-D-Val] allow a direct access to α-monofluorinated phosphonate mimetics of naturally occurring phosphoserine and Phosphothreonine, in enantiomerically pure form and suitably protected for solid-phase peptide synthesis.
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asymmetric synthesis of a protected phosphonate isostere of Phosphothreonine for solid phase peptide synthesis
Tetrahedron Letters, 1994Co-Authors: María José Ruiz, Vicente Ojea, Gideon Shapiro, Hans Peter Weber, Esteban PombovillarAbstract:Abstract The first enantiospecific synthesis of 2 , a phosphonate isostere of Phosphothreonine suitably protected for solid-phase peptide synthesis, has been achieved by coupling the highly face-selective conjugate addition of the lithium salt of Schollkopf's bislactim ether to E -prop-2-enyl-phosphonates with a selective enzymatic carboxylic ester hydrolysis. The absolute configuration of the products has been assigned from the X-ray structure of the adduct 9c .
Vicente Ojea - One of the best experts on this subject based on the ideXlab platform.
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stereoselective synthesis of α monofluorinated phosphonate mimetics of naturally occurring phosphoserine and Phosphothreonine via electrophilic fluorination of lithiated bis lactim ethers
Chemical Communications, 2002Co-Authors: María José Ruiz, Vicente Ojea, Jose M Quintela, Juan J GuillinAbstract:Electrophilic fluorinations of lithiated bis-lactim ethers derived from cyclo-[L-AP4-D-Val] allow a direct access to α-monofluorinated phosphonate mimetics of naturally occurring phosphoserine and Phosphothreonine, in enantiomerically pure form and suitably protected for solid-phase peptide synthesis.
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stereoselective synthesis of alpha monofluorinated phosphonate mimetics of naturally occurring phosphoserine and Phosphothreonine via electrophilic fluorination of lithiated bis lactim ethers
Chemical Communications, 2002Co-Authors: María José Ruiz, Vicente Ojea, Jose M Quintela, Juan J GuillinAbstract:Electrophilic fluorinations of lithiated bis-lactim ethers derived from cyclo-[L-AP4-D-Val] allow a direct access to α-monofluorinated phosphonate mimetics of naturally occurring phosphoserine and Phosphothreonine, in enantiomerically pure form and suitably protected for solid-phase peptide synthesis.
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asymmetric synthesis of a protected phosphonate isostere of Phosphothreonine for solid phase peptide synthesis
Tetrahedron Letters, 1994Co-Authors: María José Ruiz, Vicente Ojea, Gideon Shapiro, Hans Peter Weber, Esteban PombovillarAbstract:Abstract The first enantiospecific synthesis of 2 , a phosphonate isostere of Phosphothreonine suitably protected for solid-phase peptide synthesis, has been achieved by coupling the highly face-selective conjugate addition of the lithium salt of Schollkopf's bislactim ether to E -prop-2-enyl-phosphonates with a selective enzymatic carboxylic ester hydrolysis. The absolute configuration of the products has been assigned from the X-ray structure of the adduct 9c .