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Mar Drugs
2019 Mar 27;174:. doi: 10.3390/md17040195.
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Precise Structure and Anticoagulant Activity of Fucosylated Glycosaminoglycan from Apostichopus japonicus: Analysis of Its Depolymerized Fragments.
Guan R
,
Peng Y
,
Zhou L
,
Zheng W
,
Liu X
,
Wang P
,
Yuan Q
,
Gao N
,
Zhao L
,
Zhao J
.
Abstract
Apostichopus japonicus is one of the most economically important species in sea cucumber aquaculture in China. Fucosylated glycosaminoglycan from A. japonicus (AjFG) has shown multiple pharmacological activities. However, results from studies on the structure of AjFG are still controversial. In this study, the deaminative depolymerization method that is glycosidic bond-selective was used to prepare the depolymerized products from AjFG (dAjFG), and then a series of purified oligosaccharide fragments such as tri-, hexa-, nona-, and dodecasaccharides were obtained from dAjFG by gel permeation chromatography. The 1D/2D NMR and ESI-MS spectrometry analyses showed that these oligosaccharides had the structural formula of l-FucS-α1,3-d-GlcA-β1,3-{d-GalNAc4S6S-β1,4-[l-FucS-α1,3-]d-GlcA-β1,3-}
n
-d-anTal-diol4S6S (n = 0, 1, 2, 3; FucS represents Fuc2S4S, Fuc3S4S, or Fuc4S). Thus, the unambiguous structure of native AjFG can be rationally deduced: it had the backbone of {-4-d-GlcA-β1,3-d-GalNAc4S6S-β1-}
n
, which is similar to chondroitin sulfate E, and each d-GlcA residue in the backbone was branched with a l-FucS monosaccharide at O-3. Bioactivity assays confirmed that dAjFG and nonasaccharides and dodecasaccharides from AjFG had potent anticoagulant activity by intrinsic FXase inhibition while avoiding side effects such as FXII activation and platelet aggregation.
31600649, 81773737, 81703374 National Natural Science Foundation of China, CTZ18015 Fundamental Research Funds for the Central University, 2016ACA138 Key Projects of Technological Innovation of Hubei Province
Figure 1. Physicochemical properties of AjFG, dAjFG, and the purified fragments. HPLC profiles of AjFG (a), dAjFG (a and b) and the oligosaccharide fragments with various dp (c) (A); chromatograms of PMP derivatives of mixed monosaccharide standards (a) and AjFG (b) (B); and FI-IR spectrum of AjFG (C).
Figure 2. 1H-13C HSQC (A) and superimposed 1H-1H COSY (black), TOCSY (red), and ROESY (green) (B) spectra of Fragment 1 (Fr-1). I and II represent type I and II of FucS, respectively. UI, UII, TI, and TII represent the GlcA and anTal-diol residues substituted with type I and II of FucS, respectively.
Figure 3. The effects of AjFG, dAjFG and oligosaccharides with various dp (Fr-1–Fr-4) on APTT (A), intrinsic FXase (B), and human factor XII activation (C). The results were expressed as mean ± SD (n = 2).
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