130548-92-4Relevant articles and documents
Nanodisk-based glioma-targeted drug delivery enabled by a stable glycopeptide
Wang, Huan,Wang, Xiaoyi,Xie, Cao,Zhang, Mingfei,Ruan, Huitong,Wang, Songli,Jiang, Kuan,Wang, Fei,Zhan, Changyou,Lu, Weiyue,Wang, Hao
, p. 26 - 38 (2018)
Heptapeptide ATWLPPR (A7R) binds specifically to vascular endothelial growth factor receptor 2 (VEGFR2) and neuropilin-1 (NRP-1) overexpressed in glioma cells, exhibiting high potential to achieve glioma targeted drug delivery. However, in vivo application of A7R peptide remains challenging due to the poor proteolytic stability and inaccessibility of A7R to the brain. To tackle these problems, we identified a glycosylated A7R derivative to enhance in vivo stability and brain transport efficacy. Our results showed that glycosylation of peptide could efficiently improve stability in serum, traverse the blood-brain barrier (BBB) and be uptaken by glioma cells. Furthermore, a novel glioma-targeted drug delivery system was constructed successfully employing glycopeptide as the targeting moiety and nanodisk as the carrier of paclitaxel (PTX). Physicochemical characterization showed that the nanodisk presented suitable size of 50 nm and adequate loading capacity of PTX. Compared to non-glycosylated nanodisk, glycopeptide modification could significantly enhance the uptake of disks by brain capillary endothelial cells through glucose transporter 1 (GLUT1). In vivo imaging and glioma fluorescence section results also indicated that nanodisks modified with glycopeptide showed a higher accumulation in glioma. The glycopeptide-enabled PTX delivery system exhibited superior anti-glioma efficacy in intracranial glioma xenograft model. These results suggested that glycosylation of peptides provided an efficient pathway to design multifunctional and stable brain targeting ligands.
Glycosylation of α-amino acids by sugar acetate donors with InBr 3. Minimally competent Lewis acids
Lefever, Mark R.,Szab, Lajos Z.,Anglin, Bobbi,Ferracane, Michael,Hogan, Joanna,Cooney, Lauren,Polt, Robin
body text, p. 121 - 125 (2012/05/20)
A simplified method for the preparation of Fmoc-serine and Fmoc-threonine glycosides for use in O-linked glycopeptide synthesis is described. Lewis acids promote glycoside formation, but also promote undesired reactions of the glycoside products. Use of 'minimally competent' Lewis acids such as InBr 3 promotes the desired activation catalytically, and with greatly reduced side products from sugar peracetates.
Glycosylated analogs of formaecin I and drosocin exhibit differential pattern of antibacterial activity
Talat, Sariya,Thiruvikraman, Menithalakshmi,Kumari, Saroj,Kaur, Kanwal J.
, p. 537 - 555 (2014/02/14)
The synthetic glycopeptides are interesting model systems to study the effect of O-glycosylation in modulating their function and structure. A series of glycosylated analogs of two antibacterial peptides, formaecin I and drosocin, were synthesized by varying the nature of sugar and its linkage with bioactive peptides to understand the influence of structure variation of glycosylation on their antibacterial activities. Higher antibacterial activities of all glycopeptides compared to their respective non-glycosylated counterparts emphasize in part the importance of sugar moieties in functional implications of these peptides. The consequences of the unique differences among the analogs were apparent on their antibacterial activities but not evident structurally by circular dichroism studies. We have shown that differently glycosylated peptides exhibit differential effect among each other when tested against several Gram-negative bacterial strains. The change of monosaccharide moiety and/or its anomeric configuration in formaecin I and drosocin resulted into decrease in the antibacterial activity in comparison to that of the native glycopeptide, but the extent of decrease in antibacterial activity of glycosylated drosocin analogs was less. Probably, the variation in peptide conformation arising due to topological dissimilarities among different sugars in the same peptide resulting in possible modulation in binding properties appears to be responsible for differences in their antibacterial activities. Indeed, these effects of glycosylation are found to be sequence-specific and depend in the milieu of amino acid residues. Interestingly, none of the carbohydrate variants affected the basic property of these peptides, which is non-hemolytic and non-toxicity to eukaryotic cells. The Author(s) 2011.
Oxytocin analogues with O-glycosylated serine and threonine in position 4
Marcinkowska,Borovickova,Slaninova,Grzonka
, p. 1335 - 1344 (2008/09/19)
Oxytocin structure was modified in position 4 using glycoamino acids. Procedure for transformation of Fmoc-protected serine and threonine derivatives into appropriate O-glycosylated precursors suitable for solid phase peptide synthesis (SPPS) was worked o
Solid-phase synthesis of O-linked glycopeptide analogues of enkephalin
Mitchell,Pratt,Hruby,Polt
, p. 2327 - 2342 (2007/10/03)
The synthesis of 18 N-α-FMOC-amino acid glycosides for solid-phase glycopeptide assembly is reported. The glycosides were synthesized either from the corresponding O'Donnell Schiff bases or from N-α-FMOC-amino protected serine or threonine and the appropriate glycosyl bromide using Hanessian's modification of the Koenigs-Knorr reaction. Reaction rates of D-glycosyl bromides (e.g., acetobromoglucose) with the L- and D-forms of serine and threonine are distinctly different and can be rationalized in terms of the steric interactions within the two types of diastereomeric transition states for the D/L and D/D reactant pairs. The N-α-FMOC-protected glycosides [monosaccharides Xyl, Glc, Gal, Man, GlcNAc, and GalNAc; disaccharides Gal-β(1-4)-Glc (lactose), Glc-β(1-4)-Glc (cellobiose), and Gal-α(1-6)-Glc (melibiose)] were incorporated into 22 enkephalin glycopeptide analogues. These peptide opiates bearing the pharmacophore H-Tyr-c[DCys-Gly-Phe-DCys]- were designed to probe the significance of the glycoside moiety and the carbohydrate-peptide linkage region in blood-brain barrier (BBB) transport, opiate receptor binding, and analgesia.
Solid phase synthesis of O-glycoopioid peptides related to dermorphin
Sivanandaiah,Suresh Babu,Shankaramma
, p. 760 - 767 (2007/10/03)
Glycosylation of Fmoc-hydroxyamino acids with β-D-glucose pentaacetate has been carried out in the presence of several Lewis acids and BF3.Et2O has been found to be the most suitable one. Thus, 2,3,4,6-tetra-O-acetyl-β-D-glycopyranosyl derivatives of Fmoc-Ser/Thr/Tyr are prepared in a single step in reasonably good yields and high purity. The O-glycosylated derivatives are then converted to their corresponding trichlorophenyl esters for use in the solid phase synthesis of five glycoopioid peptides related to dermorphin. The effect of glycosylation on biological activity of dermorphin has been studied. Among the peptides synthesized, [Tyr(β-D-Glc)5]dermorphin and [Ser(β-D-Glc)5, Tyr7)]dermorphin exhibit considerable analgesic activity of about 80-90% compared to morphine and antidiarrhoeal activity of about 50% compared to dermorphin.
Glycosylation of Fmoc amino acids: Preparation of mono- and di-glycosylated derivatives and their incorporation into Arg-Gly-Asp (RGD)-containing glycopeptides
Vegad, Hiran,Gray, Charles J.,Somers, Peter J.,Dutta, Anand S.
, p. 1429 - 1441 (2007/10/03)
Compounds containing O-glycosidic linkages between carbohydrate species (D-glucopyranose, D-mannopyranose and L-rhamnopyranose) and hydroxy-containing amino acid components (L-threonine, L-serine and L-hydroxyproline) have been synthesized. Significant qu
Improved method for the synthesis of o-glycosylated fmoc amino acids to be used in solid-phase glycopeptide synthesis (Fmoc = fluoren-9-ylmethoxycarbonyl)
De La Torre, Beatriz G.,Torres, Josep L.,Bardaji, Eduard,Clapes, Pere,Xaus, Nuria,Jorba, Xavier,Calvet, Silvia,Albericio, Fernando,Valencia, Gregorio
, p. 965 - 967 (2007/10/02)
The building blocks O1-(2,3,4,6-tetra-O-acetyl-β-D- galactopyranosyl)-Nα(fluoren-9-ylmethoxycarbonyl)serine (5)and O 1-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl) -Nα-(fluoren-9-ylmethoxycarbonyl)threonine (6) for use in solid-phase glycopeptide synthesis can be obtained via their ally esters by mild treatment with tetrakis(triphenylphosphine)palladium(0) and tributyltin hydride with no Fmoc elimination or sugar cleavage or anomerization.
