125878-06-0Relevant articles and documents
Bisubstrate Ether-Linked Uridine-Peptide Conjugates as O-GlcNAc Transferase Inhibitors
Makwana, Vivek,Ryan, Philip,Malde, Alpeshkumar K.,Anoopkumar-Dukie, Shailendra,Rudrawar, Santosh
, p. 477 - 483 (2021)
The O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is a master regulator of installing O-GlcNAc onto serine or threonine residues on a multitude of target proteins. Numerous nuclear and cytosolic proteins of varying functional classes, including translational factors, transcription factors, signaling proteins, and kinases are OGT substrates. Aberrant O-GlcNAcylation of proteins is implicated in signaling in metabolic diseases such as diabetes and cancer. Selective and potent OGT inhibitors are valuable tools to study the role of OGT in modulating a wide range of effects on cellular functions. We report linear bisubstrate ether-linked uridine-peptide conjugates as OGT inhibitors with micromolar affinity. In vitro evaluation of the compounds revealed the importance of donor substrate, linker and acceptor substrate in the rational design of bisubstrate analogue inhibitors. Molecular dynamics simulations shed light on the binding of this novel class of inhibitors and rationalized the effect of amino acid truncation of acceptor peptide on OGT inhibition.
A gulose moiety contributes to the belomycin (BLM) disaccharide selective targeting to lung cancer cells
Cao, Yongjun,Chen, Wenming,Huang, Weiping,Li, Houkai,Liao, Guohao,Qi, Dongxia,Wang, Meizhu,Wang, Xiaoyang,Ye, Wenchong,Zhou, Cui,Zhou, Wen
, (2021/10/07)
Eight mono- or disaccharide analogues derived from BLM disaccharide, along with the corresponding carbohydate-dye conjugates have been designed and synthesized in this study, aiming at exploring the effect of a gulose residue on the cellular binding/uptake of BLM disaccharide and it possible uptake mechanism. Our evidence is presented indicating that, for the cellular binding/uptake of BLM disaccharide, a gulose residue is an essential subunit but unrelated to its chemical nature. Interestingly, D-gulose-dye conjugate is able to selectively target A549 cancer cells, but L-gulose-dye conjugate fails. Further uptake mechanism studies demonstrate D-gulose-dye derivatives similar to BLM disaccharide-dye ones behave in a temperature- and ATP-dependent manner, and are partly directed by the GLUT1 receptor. Moreover, D-gulose modifying gemcitabine 53a exhibits more potent antitumor activity compared to derivatives 53b-c in which gemcitabine is decorated with other monosaccharides. Taken together, the monosacharide D-gulose conjugate offers a new strategy for solving cytotoxic drugs via the increased tumor targeting in the therapy of lung cancer.
Using N-nitrosodichloroacetamides to conveniently convert linear primary amines into alcohols
Macarthur, Nicholas S.,Wang, Linshu,Mccarthy, Blaine G.,Jakobsche, Charles E.
, p. 2014 - 2021 (2015/08/18)
The reported rearrangement of N-nitrosodichloroacetamides provides a practicalmethod for converting primary amines into primary alcohols. The reaction sequence is operationally simple, requires only a single purification, and is compatible with a number of common functional groups. Mechanistic studies of the nitrosylation and rearrangement reactions illustrate the increased utility of dichloroacetamides compared to various other amides for this transformation.
Ruthenium-catalyzed highly chemoselective hydrogenation of aldehydes
Bonomo, Lucia,Kermorvan, Laurent,Dupau, Philippe
, p. 907 - 910 (2015/03/18)
The use of a [(ethylenediamine)(dppe)Ru(OCOtBu)2] [dppe=1,2-bis(diphenylphosphino)ethane] complex under base-free conditions allowed highly efficient and selective hydrogenation of aldehydes in the presence of ketones in addition to olefins. Even in the case of highly sensitive 1,6-ketoaldehydes, the desired ketoalcohols were obtained in high yields with 94-99 % overall selectivity at complete aldehyde conversion with a TON up to 30 000. The lack of requirement for strong basic co-catalysts and polar protic solvents also allowed efficient and highly chemoselective reduction of aldehydes bearing other functional groups, such as epoxides, carboxylic acids, esters, amides, and nitriles emphasizing the potential synthetic utility of the catalyst. It's all about the aldehyde: The use of [(ethylenediamine)(dppe)Ru(OCOtBu)2] [dppe=1,2-bis(diphenylphosphino)ethane] under base-free conditions allows highly efficient and selective hydrogenation of aldehydes in the presence of ketones. Highly selective hydrogenation of additional aldehydes in the presence of other functional groups, such as epoxides, carboxylic acids, esters, amides, and nitriles emphasizes the potential synthetic utility of the catalyst.
Synthetic 1-deoxynojirimycin N-substituted peptides offer prolonged disruption to N-linked glycan processing
Aguilar, Aim Lpez,Escribano, Jaime,Wentworth, Paul,Butters, Terry D.
supporting information, p. 2809 - 2813 (2015/02/02)
A panel of 1-deoxynojirimycin (DNJ) N-linked peptides were synthesized. Their IC50 values were measured in vitro against a-glucosidases I and II and were found to be in the micromolar range for both isozymes, and better than that of the iminosugar NB-DNJ (miglustat, 3) against a-glucosidase II. Cell-based studies revealed that although the free iminosugar 3 is most effective at disrupting N-linked glycan processing for shortterm incubations (one day), when the cell-based studies were extended to three days, the DNJ N-linked tetrapeptide KDEL, which is an endoplasmic reticulum (ER)-retaining sequence, performed far better than 3. In low inhibitor washout studies, NB-DNJ inhibition was decreased to zero after 24 h, but DNJ- KDEL retained 13% activity. This method offers a general approach for targeting drugs to the ER and prolonging their activity. Moreover, it is modular, so as new iminosugars of increased potency are discovered, they can be added to this template for targeting.
Synthesis and characterization of well-defined l-lactic acid-caprolactone co-oligomers and their rhenium (I) and technetium(I) conjugates
Zhu, Hua,Yang, Zhi,Li, Nan,Wang, Xue-Juan,Wang, Feng,Su, Hua,Xie, Qing,Zhang, Yan,Ma, Yun-Xia,Lin, Bao-He
, p. 95 - 102 (2012/11/13)
Staring from l-lactide and ε-caprolactone, the corresponding lactic-caprolactone cooligomer with hydroxyl and carboxylic acid groups were synthesized. These oligomers were connected with chelating groups through a long chain tether, ready for transition metal binding. Coordination of organometallic rhenium(I) and technetium(I) complexes generated the conjugates in high yield and short time, satisfying the requirements for short-lived radiopharmaceuticals in clinical applications. A reasonable pharmacophore model has been established to guide the design of well-defined lactic acid oligomer for nuclear medicine.
E-POLYLYSINE CONJUGATES AND THE USE THEREOF
-
, (2012/05/21)
The present invention relates to ε-polylysine conjugates, in particular conjugates of ε-polylysine with compounds carrying carboxyl groups, and to the preparation and use thereof for targeting of the kidney.
Molecularly defined caprolactone oligomers and polymers: Synthesis and characterization
Takizawa, Kenichi,Tang, Chuanbing,Hawker, Craig J.
, p. 1718 - 1726 (2008/09/18)
The synthesis of molecularly defined ε-caprolactone oligomers and polymers up to the 64-mer, via an exponential growth strategy, is described. By careful selection of orthogonal protecting groups, t-butyldimethylsilyl (TBDMS) ether for the hydroxyl group and benzyl (Bn) ester for the carboxylic acid group, a highly efficient synthetic strategy was developed with yields for both deprotection steps being essentially quantitative and for the coupling reactions using 1,3-dicyclohexylcarbodiimide (DCC), yields of 80-95% were obtained even at high molecular weights. This allows monodisperse dimers, tetramers, octamers, 16-mers, 32-mers and 64-mers to be prepared in gram quantities and fully characterized using mass spectroscopy, size exclusion chromatography (SEC), and IR and NMR spectroscopy. Thermal and physical properties were measured using thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), atomic force microscopy (AFM), and small-angle X-ray scattering (SAXS). These results conclusively show a distinct structure/property relationship with a close correlation between the number of repeat units and physical properties. In addition, a number of marked differences were observed on comparison with the parent poly(caprolactone) polymer.
Studies towards a conjugate vaccine for anthrax: Synthesis of the tetrasaccharide side chain of the Bacillus anthracis exosporium
Adamo, Roberto,Saksena, Rina,Kovac, Pavol
, p. 1075 - 1089 (2007/10/03)
The first synthesis of β-L-glycoside 17 of the tetrasaccharide β-Ant-(1 → 3)-α-L-Rhap-(1 → 3)-α-L-Rhap-(1 → 2)-L-Rhap is described (Schemes 1-3). Its spacer can be functionalized to make it amenable to conjugation to proteins by different conjugation meth
Synthesis, characterization, and properties of phosphoryl choline functionalized poly ε-caprolactone and charged phospholipid analogues
Nederberg, Fredrik,Bowden, Tim,Hilborn, Joens
, p. 954 - 965 (2007/10/03)
Here, we introduce the synthesis, characterization, and surface orientation properties of a new generation of biodegradable and biomimetic polymers. These phospholipid-mimetic, biodegradable polymers are synthesized by combining poly ε-caprolactone (PCL)
