118358-80-8Relevant articles and documents
Antibacterial cyclic D,L-α-glycopeptides
Motiei, Leila,Rahimipour, Shai,Thayer, Desiree A.,Wong, Chi-Huey,Ghadiri, M. Reza
, p. 3693 - 3695 (2009)
We report the design, synthesis, membrane activity, biophysical characterization, and in vitro antibacterial activities of cationic cyclic d,l-α-glycopeptides bearing d-glucosamine (GlcNH2), d-galactose (Gal), or d-mannose (Man) glycosyl side chains.
Orthogonal solid-phase synthesis of tetramannosylated peptide constructs carrying three independent branched epitopes
Kragol, Goran,Otvos Jr., Laszlo
, p. 957 - 966 (2001)
The development of peptide-based drugs requires the chemical synthesis of systems as complex as they appear in nature. Most bioactive peptides have to be associated with co-activators and delivery or targeting domains, the synthesis of such complexes is far from trivial. In efforts to develop a prototype for a new generation of peptide vaccines, a peptide construct was prepared, using an alternating lysine and glycine backbone. A 24-mer major antigen corresponding to the M2 protein of influenza virus, and two shorter T-cell epitopes derived from the hemagglutinin were co-synthesized onto the side chains of the first three lysines. To help the delivery of the constructs inside the antigen presenting cells via the multimeric cell surface mannose receptor, three additional lysines were decorated with four mannosylated serine residues. The synthesis difficulty increased upon addition of the glycoamino acids and alternating the peptide and glycoamino acid branches. The successful solid-phase synthesis of the constructs proceeded with the use of a combination of three quasi-orthogonally removable amino protecting groups and a robust activation strategy. These multi-glycosylated constructs represent some of the most complex synthetic peptides to date, and will be used to study the entire process of antigen delivery, presentation and immunogenicity.
Synthesis of high functionality and quality mannose-grafted lipids to produce macrophage-targeted liposomes
Hagimori, Masayori,Chinda, Yorinao,Suga, Tadaharu,Yamanami, Kazuto,Kato, Naoya,Inamine, Tatsuo,Fuchigami, Yuki,Kawakami, Shigeru
, p. 153 - 161 (2018)
The mannose receptor, which is responsible for tumor invasion, proliferation, and metastasis in the tumor microenvironment, is overexpressed in tumor-associated macrophages. Mannose is commonly applied to PEGylated liposomes in macrophage-targeted cancer therapy. To develop a high functionality and quality (HFQ) lipid for macrophage-targeted liposomes, we designed a novel mannosylated lipid with improved mannose receptor binding affinity using serine–glycine repeats (SG)n. We synthesized Man(S)-(SG)5-SSK-K(Pal)2 using only a fluorenylmethyloxycarbonyl (Fmoc) protecting group solid-phase peptide synthesis method, which produced a high-quality lipid at a moderately good yield. We then prepared Man-(SG)5/PEGylated liposomes using a post-insertion technique to insert Man(S)-(SG)5-SSK-K(Pal)2 into the PEGylated liposomes. In vitro cell investigations revealed that the Man-(SG)5/PEGylated liposomes effectively associated with mouse peritoneal macrophages by interacting with the mannose receptors. The results suggest that we produced a novel high-quality, highly functional mannosylated lipid that is suitable for clinical drug delivery applications.
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.
A convenient and efficient synthetic approach to mono-, di-, and tri-O-mannosylated Fmoc amino acids
Chen, Liqun,Tan, Zhongping
supporting information, p. 2190 - 2193 (2013/04/24)
A convenient and highly efficient synthesis of mono-, di-, and tri-O-mannosylated Fmoc-Ser and Thr is described. The short synthetic route and high overall yield highlight the synthetic utility of this unified approach.
Synthesis of serine-based glycolipids as potential TLR4 activators
Huang, Li-De,Lin, Hong-Jyune,Huang, Po-Hsiung,Hsiao, Wei-Chen,Raghava Reddy, L. Vijaya,Fu, Shu-Ling,Lin, Chun-Cheng
scheme or table, p. 2492 - 2504 (2011/05/14)
A new series of monosaccharide-based glycolipids devoid of phosphate groups and with two lipid chains were rationally designed by varying the lipid chain lengths and saccharide structure of a α-GalCer-derived lead compound (CCL-34) that is a potent TLR4 agonist. The NF-κB activity of a 60-membered galactosyl serine-based synthetic library containing compounds with various lipid chain lengths was measured in a HEK293 cell line that stably expressed human TLR4, MD2, and CD14 (293-hTLR4/MD2-CD14). The results showed that the optimal carbon chain lengths for the lipid amine and fatty acid to activate TLR4 were 10-11 and 12, respectively. Evaluation of a 20-membered synthetic glycosyl serine-based lipid library containing compounds with various saccharide moieties and fixed lipid chain lengths revealed that the galactose moiety in CCL-34 could be replaced by glucose without loss of activity (CCL-34-S3 and CCL-34-S16). Changing the orientation of the anomeric glycosidic bond of CCL-34 resulted in a complete loss of activity (β-CCL34). Surprisingly, a change in configuration of the anomeric glycosidic bond in a glucosyl glycolipid is tolerable (CCL-34-S14). Another noteworthy observation is that the activity of a l-fucosyl derived glycolipid (CCL-34-S13) was comparable to that of CCL-34. In sum, this study determines the structural features that are crucial for an optimal TLR4-stimulating activity. It also provides several molecules with immunostimulating potential.
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.
Studies toward the site specific incorporation of sugars into proteins: Synthesis of glycosylated aminoacyl-tRNAs
Fahmi, Nour Eddine,Golovine, Serguei,Wang, Bixun,Hecht, Sidney M.
, p. 149 - 164 (2007/10/03)
A series of glycosylated serine derivatives was synthesized from peracetylated sugars and Fmoc-protected serine; these were chemically esterified with the tris-(tetrabutylammonium) salt of pdCpA. The fully protected and deprotected glycosylated aminoacyl pdCpAs were ligated enzymatically to an abbreviated tRNA (tRNA-COH) to provide the title compounds that are key intermediates in the elaboration of glycoproteins using readthrough of a nonsense codon.
Studies on selectin blockers. 7. Structure-activity relationships of sialyl Lewis X mimetics based on modified ser-glu dipeptides
Tsukida, Takahiro,Moriyama, Hideki,Kurokawa, Kiriko,Achiha, Toshio,Inoue, Yoshimasa,Kondo, Hirosato
, p. 4279 - 4287 (2007/10/03)
We have previously found that heterochiral fucodipeptides, L-Ser-D-Glu (3a) and D-Ser-L-Glu (3b), exhibited up to 20-100 times more potency than a sialyl Lewis X (sLe(X), 1) and a 3'sulfated Lewis X analogue (2) toward E- selectin binding and have also proposed, from molecular dynamics calculation, that their strong activities would depend on a possible formation of the type II and/or type II' β-turn of compounds 3a,b (Tsukida, T.; Hiramatsu, Y.; Tsujishita, H.; Kiyoi, T.; Yoshida, M.; Kurokawa, K.; Moriyama, H.; Ohmoto, H.; Wada, Y.; Saito, T.; Kondo, H. J. Med. Chem. 1997, 40, 3534-3541). To clarify our hypothesis, we synthesized several analogues of compounds 3a,b and investigated their structure-activity relationships. As a result, it was indicated that the type II and/or type II' β-turn conformation would be a comparatively tight form and would play important roles in favorable binding to E-selectin. These findings indicate that sLe(X) mimetics with type II and type II' β-turn dipeptides could be a useful methodology for the design of an active selectin blocker.
