160067-63-0Relevant articles and documents
Insights into the geometrical features underlying β-O-GIcNAc glycosylation: Water pockets drastically modulate the interactions between the carbohydrate and the peptide backbone
Fernandez-Tejada, Alberto,Corzana, Francisco,Busto, Jesus H.,Jimenez-Oses, Gonzalo,Jimenez-Barbero, Jesus,Avenoza, Alberto,Peregrina, Jesus M.
, p. 7297 - 7301 (2009)
A novel and simple model was proposed to explain the different relative orientation of the peptide backbone and presentation of beta-N-scetyl-D- glucosamine (β-O-GlcNAc)-Thr and Ser moieties. The sugar-peptide interactions were modulated by the specific hydrogen bonds and the existence of water pockets at key sites. NMR experiments of the interactions were recorded on a Bruker Avance 400 spectrometer at 298 K to verify the investigations. MAD-tar simulations were performed with AMBER 6.0 (AMBER94) that was implemented with GLYCAM 04 parameters to accurately simulate the computational behavior of the sugar moiety. NOE-derived distances were included as time-averaged coupling constraints along with the scalar coupling constants J. Final trajectories were run using an exponential decay constant of 16 ns and a simulation length of 16 ns with water molecules.
Synthesis, biological evaluation and structural characterization of novel glycopeptide analogues of nociceptin N/OFQ
Arsequell, Gemma,Rosa, Monica,Mayato, Carlos,Dorta, Rosa L.,Gonzalez-Nunez, Veronica,Barreto-Valer, Katherine,Marcelo, Filipa,Calle, Luis P.,Vazquez, Jesus T.,Rodriguez, Raquel E.,Jimenez-Barbero, Jesus,Valencia, Gregorio
, p. 6133 - 6142 (2011)
To examine if the biological activity of the N/OFQ peptide, which is the native ligand of the pain-related and viable drug target NOP receptor, could be modulated by glycosylation and if such effects could be conformationally related, we have synthesized three N/OFQ glycopeptide analogues, namely: [Thr5-O-α-d-GalNAc-N/OFQ] (glycopeptide 1), [Ser 10-O-α-d-GalNAc]-N/OFQ (glycopeptide 2) and [Ser 10-O-β-d-GlcNAc]-N/OFQ] (glycopeptide 3). They were tested for biological activity in competition binding assays using the zebrafish animal model in which glycopeptide 2 exhibited a slightly improved binding affinity, whereas glycopeptide 1 showed a remarkably reduced binding affinity compared to the parent compound and glycopeptide 3. The structural analysis of these glycopeptides and the parent N/OFQ peptide by NMR and circular dichroism indicated that their aqueous solutions are mainly populated by random coil conformers. However, in membrane mimic environments a certain proportion of the molecules of all these peptides exist as α-helix structures. Interestingly, under these experimental conditions, glycopeptide 1 (glycosylated at Thr-5) exhibited a population of folded hairpin-like geometries. From these facts it is tempting to speculate that nociceptin analogues showing linear helical structures are more complementary and thus interact more efficiently with the native NOP receptor than folded structures, since glycopeptide 1 showed a significantly reduced binding affinity for the NOP receptor.
Practical synthesis of the 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucosides of Fmoc-serine and Fmoc-threonine and their benzyl esters
Carvalho, Ivone,Scheuerl, Shona L.,Kartha, K.P. Ravindranathan,Field, Robert A.
, p. 1039 - 1043 (2003)
Mercuric bromide-promoted glycosylation of Fmoc-Ser-OBn and Fmoc-Thr-OBn with 2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-α-D-glucopyranosyl chloride in refluxing 1,2-dichloroethane gave the corresponding β-glycosides in good yields (64 and 62%, respectively).
A silyl ether-protected building block forO-GlcNAcylated peptide synthesis to enable one-pot acidic deprotection
Yan, Bingjia,Li, Wenyi,Hackenberger, Christian P. R.
supporting information, p. 8014 - 8017 (2021/10/04)
In this report, we introduce a novel building block for Fmoc/tBu solid phase peptide synthesis (SPPS) of β-linkedO-GlcNAcylated peptides. This building block carries acid labile silyl ether protecting groups, which are fully removed under TFA-mediated peptide cleavage conditions from the resin, thus requiring fewer synthetic steps and no intermediate purification as compared to other acid or base labile protecting group strategies.
Effects of Glycosylation and d -Amino Acid Substitution on the Antitumor and Antibacterial Activities of Bee Venom Peptide HYL
Wu, Ming-Hao,Ai, Su,Chen, Qing,Chen, Xiang-Yan,Li, Hong-Jin,Li, Yu-Lei,Zhao, Xia
, p. 2293 - 2302 (2020/11/26)
Glycosylation is a promising strategy for modulating the physicochemical properties of peptides. However, the influence of glycosylation on the biological activities of peptides remains unknown. Here, we chose the bee venom peptide HYL as a model peptide and 12 different monosaccharides as model sugars to study the effects of glycosylation site, number, and monosaccharide structure on the biochemical properties, activities, and cellular selectivities of HYL derivatives. Some analogues of HYL showed improvement not only in cell selectivity and proteolytic stability but also in antitumor and antimicrobial activity. Moreover, we found that the helicity of glycopeptides can affect its antitumor activity and proteolytic stability, and the α-linked d-monosaccharides can effectively improve the antitumor activity of HYL. Therefore, it is possible to design peptides with improved properties by varying the number, structure, and position of monosaccharides. What's more, the glycopeptides HYL-31 and HYL-33 show a promising prospect for antitumor and antimicrobial drugs development, respectively. In addition, we found that the d-lysine substitution strategy can significantly improve the proteolytic stability of HYL. Our new approach provides a reference or guidance for the research of novel antitumor and antimicrobial peptide drugs.
Improving Selectivity, Proteolytic Stability, and Antitumor Activity of Hymenochirin-1B: A Novel Glycosylated Staple Strategy
Li, Yulei,Zhang, Yihan,Wu, Minghao,Chang, Qi,Hu, Honggang,Zhao, Xia
, p. 516 - 525 (2019/03/11)
As a host defense peptide, hymenochirin-1B has attracted increasing attention for its strong cytotoxic activities. However, its poor selectivity and proteolytic stability remain major obstacles for clinical application. To solve these problems, we designed and synthesized a series of peptide analogues of hymenochirin-1B based on cationic residue substitution and stapling combined with a glycosylation strategy. Some analogues showed improvement not only in selectivity and proteolytic stability but also in antitumor activity. Among them, the glycosylated stapled peptide H-58 was identified as the most potential antitumor peptide. Flow cytometry and a competitive binding assay revealed that H-58 displayed significant antitumor selectivity. Confocal microscopy and nuclear staining with Hoechst dye demonstrated that H-58 entered the nucleus and caused DNA damage. In summary, the strategy of glycosylated stapled peptides is a promising approach for improving the antitumor selectivity, proteolytic stability, and antitumor activity of hymenochirin-1B, which can be used for other bioactive peptide modifications.