Novel Ester-Linked Carbohydrate−Peptide Adducts: Effect of the Peptide Substituent on the Pathways of Intramolecular Reactions

Abstract

Carbohydrate−peptide conjugates in which D-glucose is linked through an ester linkage to the carboxy group of TyrPro (2), Tyr-Pro-Phe (5) or Tyr-Pro-Phe-Val (11), through the C6 hydroxy group of the sugar moiety were synthesized to examine the utility of this type of monosaccharide modification for peptide prodrugs. Evidence is provided that glycoconjugates 2, 5, and 11 easily undergo intramolecular chemical transformations, subsequent to attack of the free N-ter- [a]

Stereospecific, High-Yielding, and Green Synthesis of β-Glycosyl Esters

“…However, the yields for carbohydrate−peptide conjugations are around 30% in the literature. 39 Bile acid glycoside, which has been identified in biological materials, has been synthesized as a mixture of α-and β-anomers (ratio of α:β = 1:3) in <30% yields, and it had to be purified via HPLC. 28 However, under our reaction conditions, the β-glycoside was obtained stereospecifically in 83% yield with no chromatography ( Table 2, entry 17).…”

“…It has been reported that glycosylation can improve the properties of peptide biopharmaceuticals. ,, Therefore, three amino acid derivatives were subjected to the glucosylation conditions, and the yields were excellent (Table , entries 7, 10, and 11). However, the yields for carbohydrate–peptide conjugations are around 30% in the literature .…”

“…It has been reported that glycosylation can improve the properties of peptide biopharmaceuticals. ,, Therefore, three amino acid derivatives were subjected to the glucosylation conditions, and the yields were excellent (Table , entries 7, 10, and 11). However, the yields for carbohydrate–peptide conjugations are around 30% in the literature . Bile acid glycoside, which has been identified in biological materials, has been synthesized as a mixture of α- and β-anomers (ratio of α:β = 1:3) in <30% yields, and it had to be purified via HPLC .…”

Stereospecific, High-Yielding, and Green Synthesis of β-Glycosyl Esters

“…However, the yields for carbohydrate−peptide conjugations are around 30% in the literature. 39 Bile acid glycoside, which has been identified in biological materials, has been synthesized as a mixture of α-and β-anomers (ratio of α:β = 1:3) in <30% yields, and it had to be purified via HPLC. 28 However, under our reaction conditions, the β-glycoside was obtained stereospecifically in 83% yield with no chromatography ( Table 2, entry 17).…”

“…It has been reported that glycosylation can improve the properties of peptide biopharmaceuticals. ,, Therefore, three amino acid derivatives were subjected to the glucosylation conditions, and the yields were excellent (Table , entries 7, 10, and 11). However, the yields for carbohydrate–peptide conjugations are around 30% in the literature .…”

“…It has been reported that glycosylation can improve the properties of peptide biopharmaceuticals. ,, Therefore, three amino acid derivatives were subjected to the glucosylation conditions, and the yields were excellent (Table , entries 7, 10, and 11). However, the yields for carbohydrate–peptide conjugations are around 30% in the literature . Bile acid glycoside, which has been identified in biological materials, has been synthesized as a mixture of α- and β-anomers (ratio of α:β = 1:3) in <30% yields, and it had to be purified via HPLC .…”

Blind Separation of Analytes in Nuclear Magnetic Resonance Spectroscopy and Mass Spectrometry: Sparseness-Based Robust Multicomponent Analysis

“…It was also important to have known and wellcharacterized compounds to verify accuracy of estimation. Among many options, we have selected the 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 glycopeptides 1-4, 39 where the N-terminally protected dipeptide (Tyr-Pro, 1), tripeptides (Tyr-Pro-Phe, Blind extraction of four analytes from three mixtures in 2D NMR spectroscopy. Figures 1 to 4 and Table 1 demonstrate the experimental blind extraction of four pure-component COSY spectra from three mixtures by means of the described sparseness-based multivariate data analysis method.…”

Enediyne compounds - new promises in anticancer therapy

“…Considerable efforts have been invested in designing compounds with improved bioavailability and capability to mimic peptide functions. Laboratory for carbohydrate, peptide and glycopeptide research at the Ru|er Bo{kovi} Institute has a long tradition in the design, synthesis, analysis, conformations, dynamics and structure-activity relationship of biologically relevant peptides, glycopeptides and peptidomimetics (8)(9)(10)(11)(12)(13)(14)(15)(16). In recent years, we have been dedicated to carbohydrate-modified amino acids and peptides and found them suitable models for the study of biological phenomena (8,9,11,13,16).…”

Stereospecific, High-Yielding, and Green Synthesis of β-Glycosyl Esters

“…However, the yields for carbohydrate−peptide conjugations are around 30% in the literature. 39 Bile acid glycoside, which has been identified in biological materials, has been synthesized as a mixture of α-and β-anomers (ratio of α:β = 1:3) in <30% yields, and it had to be purified via HPLC. 28 However, under our reaction conditions, the β-glycoside was obtained stereospecifically in 83% yield with no chromatography ( Table 2, entry 17).…”

“…It has been reported that glycosylation can improve the properties of peptide biopharmaceuticals. ,, Therefore, three amino acid derivatives were subjected to the glucosylation conditions, and the yields were excellent (Table , entries 7, 10, and 11). However, the yields for carbohydrate–peptide conjugations are around 30% in the literature .…”

“…It has been reported that glycosylation can improve the properties of peptide biopharmaceuticals. ,, Therefore, three amino acid derivatives were subjected to the glucosylation conditions, and the yields were excellent (Table , entries 7, 10, and 11). However, the yields for carbohydrate–peptide conjugations are around 30% in the literature . Bile acid glycoside, which has been identified in biological materials, has been synthesized as a mixture of α- and β-anomers (ratio of α:β = 1:3) in <30% yields, and it had to be purified via HPLC .…”

Blind Separation of Analytes in Nuclear Magnetic Resonance Spectroscopy and Mass Spectrometry: Sparseness-Based Robust Multicomponent Analysis

“…It was also important to have known and wellcharacterized compounds to verify accuracy of estimation. Among many options, we have selected the 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 glycopeptides 1-4, 39 where the N-terminally protected dipeptide (Tyr-Pro, 1), tripeptides (Tyr-Pro-Phe, Blind extraction of four analytes from three mixtures in 2D NMR spectroscopy. Figures 1 to 4 and Table 1 demonstrate the experimental blind extraction of four pure-component COSY spectra from three mixtures by means of the described sparseness-based multivariate data analysis method.…”

Enediyne compounds - new promises in anticancer therapy

“…Considerable efforts have been invested in designing compounds with improved bioavailability and capability to mimic peptide functions. Laboratory for carbohydrate, peptide and glycopeptide research at the Ru|er Bo{kovi} Institute has a long tradition in the design, synthesis, analysis, conformations, dynamics and structure-activity relationship of biologically relevant peptides, glycopeptides and peptidomimetics (8)(9)(10)(11)(12)(13)(14)(15)(16). In recent years, we have been dedicated to carbohydrate-modified amino acids and peptides and found them suitable models for the study of biological phenomena (8,9,11,13,16).…”

Stereospecific, High-Yielding, and Green Synthesis of β-Glycosyl Esters

“…However, the yields for carbohydrate−peptide conjugations are around 30% in the literature. 39 Bile acid glycoside, which has been identified in biological materials, has been synthesized as a mixture of α-and β-anomers (ratio of α:β = 1:3) in <30% yields, and it had to be purified via HPLC. 28 However, under our reaction conditions, the β-glycoside was obtained stereospecifically in 83% yield with no chromatography ( Table 2, entry 17).…”

“…It has been reported that glycosylation can improve the properties of peptide biopharmaceuticals. ,, Therefore, three amino acid derivatives were subjected to the glucosylation conditions, and the yields were excellent (Table , entries 7, 10, and 11). However, the yields for carbohydrate–peptide conjugations are around 30% in the literature .…”

“…It has been reported that glycosylation can improve the properties of peptide biopharmaceuticals. ,, Therefore, three amino acid derivatives were subjected to the glucosylation conditions, and the yields were excellent (Table , entries 7, 10, and 11). However, the yields for carbohydrate–peptide conjugations are around 30% in the literature . Bile acid glycoside, which has been identified in biological materials, has been synthesized as a mixture of α- and β-anomers (ratio of α:β = 1:3) in <30% yields, and it had to be purified via HPLC .…”

Blind Separation of Analytes in Nuclear Magnetic Resonance Spectroscopy and Mass Spectrometry: Sparseness-Based Robust Multicomponent Analysis

“…It was also important to have known and wellcharacterized compounds to verify accuracy of estimation. Among many options, we have selected the 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 glycopeptides 1-4, 39 where the N-terminally protected dipeptide (Tyr-Pro, 1), tripeptides (Tyr-Pro-Phe, Blind extraction of four analytes from three mixtures in 2D NMR spectroscopy. Figures 1 to 4 and Table 1 demonstrate the experimental blind extraction of four pure-component COSY spectra from three mixtures by means of the described sparseness-based multivariate data analysis method.…”

Enediyne compounds - new promises in anticancer therapy

“…Considerable efforts have been invested in designing compounds with improved bioavailability and capability to mimic peptide functions. Laboratory for carbohydrate, peptide and glycopeptide research at the Ru|er Bo{kovi} Institute has a long tradition in the design, synthesis, analysis, conformations, dynamics and structure-activity relationship of biologically relevant peptides, glycopeptides and peptidomimetics (8)(9)(10)(11)(12)(13)(14)(15)(16). In recent years, we have been dedicated to carbohydrate-modified amino acids and peptides and found them suitable models for the study of biological phenomena (8,9,11,13,16).…”