1072107-95-9Relevant academic research and scientific papers
Synthetic glycopeptides as a designated standard in focused glycoproteomics to discover serum cancer biomarkers
Yogesh,Kamiyama, Toshiya,Ohyama, Chikara,Yoneyama, Tohru,Nouso, Kazuhiro,Kimura, Satoshi,Hinou, Hiroshi,Nishimura, Shin-Ichiro
, p. 1351 - 1358 (2018)
Previous studies on the large-scale glycomics of more than 3500 human serum samples revealed that the serum glycoproteins of cancer patients often have more dominant and specific glycoforms, namely, branched tri- and tetra-antennary N-glycans, most cancer patient groups than normal control groups. We herein established an efficient synthetic protocol of glycopeptides having highly complicated N-glycan structures that may be generated by direct tryptic digestion of serum glycoproteins. A preliminary selected reaction monitoring (SRM) assay using the synthetic model glycopeptide 1, 40Ser-Val-Gln-Glu-Ile-Gln-Ala-Thr-Phe-Phe-Tyr-Phe-Thr-Pro-Asn-Lys-Thr-Glu-Asp-Thr-Ile-Phe-Leu-Arg63 having an asialo tri-antennary N-glycan at the Asn54 residue as a designated calibration standard allowed for the rapid and absolute quantitation of the tryptic fragment derived from the serum α1-acid glycoprotein carrying a focused N-glycoform of cancer patients and healthy controls in a range between 200 and 1600 fmole μL?1 without any enrichment process for the target glycoprotein.
Chemoenzymatic glycan-selective remodeling of a therapeutic lysosomal enzyme with high-affinity M6P-glycan ligands. Enzyme substrate specificity is the name of the game
Li, Chao,Liu, Huiying,Meena, Naresh,Puertollano, Rosa,Raben, Nina,Wang, Lai-Xi,Zhang, Xiao,Zong, Guanghui
, p. 12451 - 12462 (2021/10/08)
Functionalization of therapeutic lysosomal enzymes with mannose-6-phosphate (M6P) glycan ligands represents a major strategy for enhancing the cation-independent M6P receptor (CI-MPR)-mediated cellular uptake, thus improving the overall therapeutic effica
General and Robust Chemoenzymatic Method for Glycan-Mediated Site-Specific Labeling and Conjugation of Antibodies: Facile Synthesis of Homogeneous Antibody-Drug Conjugates
Zhang, Xiao,Ou, Chong,Liu, Huiying,Prabhu, Sunaina Kiran,Li, Chao,Yang, Qiang,Wang, Lai-Xi
, p. 2502 - 2514 (2021/10/21)
Site-specific labeling and conjugation of antibodies are highly desirable for fundamental research and for developing more efficient diagnostic and therapeutic methods. We report here a general and robust chemoenzymatic method that permits a one-pot site-specific functionalization of antibodies. A series of selectively modified disaccharide oxazoline derivatives were designed, synthesized, and evaluated as donor substrates of different endoglycosidases for antibody Fc glycan remodeling. We found that among several endoglycosidases tested, wild-type endoglycosidase from Streptococcus pyogenes of serotype M49 (Endo-S2) exhibited remarkable activity in transferring the functionalized disaccharides carrying site-selectively modified azide, biotin, or fluorescent tags to antibodies without hydrolyzing the resulting transglycosylation products. This discovery, together with the excellent Fc deglycosylation activity of Endo-S2 on recombinant antibodies, allowed direct labeling and functionalization of antibodies in a one-pot manner without the need of intermediate and enzyme separation. The site-specific introduction of varied numbers of azide groups enabled a highly efficient synthesis of homogeneous antibody-drug conjugates (ADCs) with a precise control of the drug-to-antibody ratio (DAR) ranging from 2 to 12 via a copper-free strain-promoted click reaction. Cell viability assays showed that ADCs with higher DARs were more potent in killing antigen-overexpressed cells than the ADCs with lower DARs. This new method is expected to find applications not only for antibody-drug conjugation but also for cell labeling, imaging, and diagnosis.
