bims-supasi 2022-01-16 papers

Front Mol Biosci. 2021 ;8 776900

A Sulfuryl Group Transfer Strategy to Selectively Prepare Sulfated Steroids and Isotopically Labelled Derivatives.

Jaber A Alshehri, Daniel M Gill, Alan M Jones.

The treatment of common steroids: estrone, estradiol, cortisol, and pregnenolone with tributylsulfoammonium betaine (TBSAB) provides a convenient chemoselective conversion of the steroids alcohol/phenol moiety to the corresponding steroidal organosulfate. An important feature of the disclosed methodology is the millimolar scale of the reaction, and the isolation of the corresponding steroid sulfates as their biologically relevant sodium salts without the need for ion-exchange chromatography. The scope of the method was further explored in the estradiol and pregnanediol steroid systems with the bis-sulfated derivatives. Ultimately, a method to install an isotopic label, deuterium (2H) combined with estrone sulfation is a valuable tool for its mass-spectrometric quantification in biological studies.

Keywords: TBSAB; isotopic labelling; selectivity; sulfation; sulfuryl transfer

DOI: https://doi.org/10.3389/fmolb.2021.776900

Molecules. 2021 Dec 24. pii: 87. [Epub ahead of print]27(1):

Purification, Characterization, and Structural Studies of a Sulfatase from Pedobacter yulinensis.

Caleb R Schlachter, Andrea O'Malley, Linda L Grimes, John J Tomashek, Maksymilian Chruszcz, L Andrew Lee.

Sulfatases are ubiquitous enzymes that hydrolyze sulfate from sulfated organic substrates such as carbohydrates, steroids, and flavones. These enzymes can be exploited in the field of biotechnology to analyze sulfated metabolites in humans, such as steroids and drugs of abuse. Because genomic data far outstrip biochemical characterization, the analysis of sulfatases from published sequences can lead to the discovery of new and unique activities advantageous for biotechnological applications. We expressed and characterized a putative sulfatase (PyuS) from the bacterium Pedobacter yulinensis. PyuS contains the (C/S)XPXR sulfatase motif, where the Cys or Ser is post-translationally converted into a formylglycine residue (FGly). His-tagged PyuS was co-expressed in Escherichia coli with a formylglycine-generating enzyme (FGE) from Mycobacterium tuberculosis and purified. We obtained several crystal structures of PyuS, and the FGly modification was detected at the active site. The enzyme has sulfatase activity on aromatic sulfated substrates as well as phosphatase activity on some aromatic phosphates; however, PyuS did not have detectable activity on 17α-estradiol sulfate, cortisol 21-sulfate, or boldenone sulfate.

Keywords: 4-methylumbelliferyl sulfate; Pedobacter yulinensis; arylsulfatase; crystallography; formylglycine; hydrolase; sulfatase

DOI: https://doi.org/10.3390/molecules27010087

Int J Biol Macromol. 2022 Jan 05. pii: S0141-8130(21)02726-4. [Epub ahead of print]201 47-58

Preparation and characterization of 2-deacetyl-3-O-sulfo-heparosan and its antitumor effects via the fibroblast growth factor receptor pathway.

Zhengqi Zha, Yaoyao Liu, Yinghua Miao, Shiying Liao, Su-Yan Wang, Huiling Tang, Hongping Yin.

Heparosan, with a linear chain of disaccharide repeating units of → 4) β-D-glucuronic acid (GlcA) (1 → 4)-α-D-N-acetylglucosamine (GlcNAc) (1→, is a potential starting chemical for heparin synthesis. However, the chemoenzymatic synthesis of single-site sulfated heparosan and its antitumor activity have not been studied. In this study, 2-deacetyl-3-O-sulfo-heparosan (DSH) was prepared successively by the N-deacetylation chemical reaction and enzymatic modification of human 3-O-sulfotransferase-1 (3-OST-1). Structural characterization of DSH was shown the success of the sulfation with the sulfation degree of 0.87. High performance gel permeation chromatography (HPGPC) analysis revealed that DSH had only one symmetrical sharp peak with a molecular weight of 9.6334 × 104 Da. Biological function studies showed that DSH could inhibit tumor cell (A549, HepG2 and HCT116) viability and induce the apoptosis of A549 cells. Further in vitro mechanistic studies showed that DSH may induce apoptosis via the JNK signaling pathway, and the upstream signal of this process may be fibroblast growth factor receptors. These results indicated that DSH could be developed as one of a potential chemical for tumor treatment.

Keywords: 2-Deacetyl-3-O-sulfo-heparosan; Apoptosis; FGFRs; Human lung cancer A549 cell; MAPK/JNK pathway

DOI: https://doi.org/10.1016/j.ijbiomac.2021.12.098