title: Structural features of heparanase-inhibiting non-anticoagulant heparin derivative Roneparstat.
abstract: Owing to their anti-tumor and anti-inflammatory properties, non-anticoagulant glycol-split (gs) heparins, obtained by periodate oxidation/borohydride reduction, are of growing interest. The present study was focused on the structural characterization of N-acetylated gs-heparin Roneparstat, a promising anti-cancer heparanase-inhibiting drug currently being investigated in clinical trials. The major and minor structural features of structurally complex Roneparstat have been characterized for the first time using conductimetric titration, size-exclusion chromatography with triple detector array, NMR and LC/MS. It has been shown that gs-uronic acids are mainly interspersed by unmodified disaccharide building blocks, but can also be present within sequences with consequent gs-residues. Peculiar gs-sequences, such as those derived from antithrombin binding regions and those containing I2S-ANS3S6S, as well as a variety of unnatural terminal groups, markers of preparation processes, have also been identified in Roneparstat. Structural features of Roneparstat that may play an important role in interactions with proteins have been summarized.
authors.affiliation: Centro Alta Tecnologia Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni, srl, via G. Colombo, 81, 20133 Milan, Italy. Electronic address: anna.v.alekseeva@gmail.com.
authors.forename: Anna
authors.initials: A
authors.lastname: Alekseeva
authors.affiliation: Istituto di Ricerche Chimiche e Biochimiche G.Ronzoni, via G. Colombo, 81, 20133 Milan, Italy. Electronic address: giulia.mazzini@gmail.com.
authors.forename: Giulia
authors.initials: G
authors.lastname: Mazzini
authors.affiliation: Sigma-Tau Industrie Farmaceutiche Riunite S.p.A, Via Pontina, Km. 30,400, 00040 Pomezia, Italy. Electronic address: Giuseppe.Giannini@sigma-tau.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giannini
authors.affiliation: Centro Alta Tecnologia Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni, srl, via G. Colombo, 81, 20133 Milan, Italy; Istituto di Ricerche Chimiche e Biochimiche G.Ronzoni, via G. Colombo, 81, 20133 Milan, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Naggi
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D005966:Glucuronidase / Q000037:antagonists & inhibitors*; D006493:Heparin / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D010084:Oxidation-Reduction; D000099175:Heparanase
chemical_list: D004791:Enzyme Inhibitors; D005966:Glucuronidase; D006493:Heparin; D000099175:Heparanase
keywords: Anti-cancer; Glycol-split; Heparanase; Heparin; Non-anticoagulant