70428-26-1Relevant articles and documents
Development of carbohydrate-based scaffolds for restricted presentation of recognition groups. Extension to divalent ligands and implications for the structure of dimerized receptors
Murphy, Paul V.,Bradley, Helena,Tosin, Manuela,Pitt, Nigel,Fitzpatrick, Geraldine M.,Glass, W. Kenneth
, p. 5692 - 5704 (2003)
The solution structure of glycosyl amides has been studied by using NMR. A strong preference is displayed by tertiary aromatic glycosyl amides for E-anti structures in contrast with secondary aromatic glycosyl amides where Z-anti structures predominate. The structural diversity displayed by these classes of molecules would seem to be important as the directional properties of the aromatic ring, or groups attached to the aromatic ring, would be determined by choosing to have either a secondary or tertiary amide at the anomeric center and could be considered when designing bioactive molecules with carbohydrate scaffolds. The structural analysis was also carried out for related divalent secondary and tertiary glycosyl amides and these compounds display preferences similar to that of the monovalent compounds. The constrained divalent compounds have potential for promoting formation of clusters that will have restricted structure and thus have potential for novel studies of mechanisms of action of multivalent ligands. Possible applications of such compounds would be as scaffolds for the design and synthesis of ligands that will facilitate protein - protein or other receptor - receptor interactions. The affinity of restricted divalent (or higher order) ligands, designed to bind to proteins that recognize carbohydrates which would facilitate clustering and concomitantly promote protein - protein interactions, may be significantly higher than monovalent counterparts or multivalent ligands without these properties. This may be useful as a new approach in the development of therapeutics based on carbohydrates.
Study of the isomeric Maillard degradants, glycosylamine and Amadori rearrangement products, and their differentiation via MS2 fingerprinting from collision-induced decomposition of protonated ions
Wang, Shaolan,Lin, Jinsheng,Li, Dan,Huang, Tianpei,Zhu, Wenquan,Chen, Wenbin,Li, Min,Shen, Weiyang
, (2021/04/14)
Rationale: The focus of this work was to study glycosylamine and Amadori rearrangement products (ARPs), the two major degradants in the Maillard reactions of pharmaceutical interest, and utilize their MS2 fingerprints by liquid chromatography/high-resolution tandem mass spectrometry (LC/HRMS2) to quickly distinguish the two isomeric degradants. These two types of degradants are frequently encountered in the compatibility and stability studies of drug products containing primary or secondary amine active pharmaceutical ingredients (APIs), which are formulated with excipients consisting of reducing sugar functionalities. Methods: Vortioxetine was employed as the primary model compound to react with lactose to obtain the glycosylamine and ARP degradants of the Maillard reaction, and their MS2 spectra (MS2 fingerprints) were obtained by LC/MS2. Subsequently, the two degradants were isolated via preparative HPLC and their structures were confirmed by one- and two-dimensional (1D and 2D) nuclear magnetic resonance (NMR) determination. Results: The MS2 fingerprints of the two degradants display significantly different profiles, despite the fact that many common fragments are observed. Specifically, protonated glycosylamine shows a prominent characteristic fragment of [Mvort + C2H3O]+ at m/z 341 (Mvort is the vortioxetine core), while protonated ARP shows a prominent characteristic fragment of [Mvort + CH]+ at m/z 311. Further study of the Maillard reactions between several other structurally diverse primary/secondary amines and lactose produced similar patterns. Conclusions: The study suggests that the characteristic MS2 fragment peaks and their ratios may be used to differentiate the glycosylamine and ARP degradants, the two isomeric degradants of the Maillard reaction, which are commonly encountered in finished dosage forms of pharmaceutical products containing primary and secondary amine APIs.
