150438-79-2Relevant articles and documents
Design of α-S-Neoglycopeptides Derived from MUC1 with a Flexible and Solvent-Exposed Sugar Moiety
Rojas-Ocáriz, Víctor,Compa?ón, Ismael,Aydillo, Carlos,Castro-Lo?ez, Jorge,Jiménez-Barbero, Jesús,Hurtado-Guerrero, Ramón,Avenoza, Alberto,Zurbano, María M.,Peregrina, Jesús M.,Busto, Jesús H.,Corzana, Francisco
, p. 5929 - 5941 (2016)
The use of vaccines based on MUC1 glycopeptides is a promising approach to treat cancer. We present herein several sulfa-Tn antigens incorporated in MUC1 sequences that possess a variable linker between the carbohydrate (GalNAc) and the peptide backbone. The main conformations of these molecules in solution have been evaluated by combining NMR experiments and molecular dynamics simulations. The linker plays a key role in the modulation of the conformation of these compounds at different levels, blocking a direct contact between the sugar moiety and the backbone, promoting a helix-like conformation for the glycosylated residue and favoring the proper presentation of the sugar unit for molecular recognition events. The feasibility of these novel compounds as mimics of MUC1 antigens has been validated by the X-ray diffraction structure of one of these unnatural derivatives complexed to an anti-MUC1 monoclonal antibody. These features, together with potential lack of immune suppression, render these unnatural glycopeptides promising candidates for designing alternative therapeutic vaccines against cancer.
Exploration of novel macrocyclic dipeptide N-benzyl amides as proteasome inhibitors
Yu, Jianjun,Liu, Jieyu,Li, Daqiang,Xu, Lei,Hong, Duidui,Chang, Shan,Li, Jia,Liu, Tao,Zhou, Yubo
, p. 423 - 439 (2019/01/08)
As proteasome inhibitors, a series of novel macrocyclic dipeptide N-benzyl amides were designed, synthesized and evaluated. Most of them exhibited potent proteasome inhibition and excellent anti-proliferative activity against RPMI 8226, MM1S, and MV-4-11 cell lines. As the most distinguished one among this series, compound 23h displayed potent and selective proteasome inhibitory potency (IC50: β5c = 29 nM, β5i = 35 nM, β1c, β2c β1i β2i > 10 μM), excellent anti-proliferative activity against RPMI 8226, MM1S, and MV-4-11 cell lines with IC50 values of 18 nM, 15 nM, and 21 nM, respectively, as well as favorable metabolic stability in human liver microsomes (HLMs), highlighting that it is a promising lead compound for further development of proteasome inhibitors.
Synthesis and conformational analysis of neoglycoconjugates derived from O- and S-glucose
Rojas, Víctor,Carreras, Javier,Corzana, Francisco,Avenoza, Alberto,Busto, Jesús H.,Peregrina, Jesús M.
, p. 1 - 8 (2013/06/26)
Using olefin metathesis as a key step, four neoglycoconjugates incorporating α-O-glucose, α-S-glucose or β-S-glucose as a carbohydrate unit and l-serine or l-cysteine as an amino acid moiety have been synthesized. The four-atom carbon spacer allows the carbohydrate to explore a wide-ranging conformational space, which may have important implications for the molecular recognition of these molecules.
