The binding interactions of the phosphosulfomannan anticancer agent PI-88 (1) with the angiogenic growth factors FGF-1, FGF-2, and VEGF were studied by surface plasmon resonance (SPR) on a BIAcore 3000 biosensor. Compared with heparin, PI-88 has at least 11-fold higher affinity for FGF-1 and at least 3-fold higher affinity for VEGF, but at least 13-fold lower affinity for FGF-2. To define the structural features of PI-88 that are important for growth factor binding, several analogues, such as dephosphorylated PI-88 and a sulfated pentasaccharide, were prepared. The binding interactions of these analogues with FGF-1, FGF-2, and VEGF were similarly studied by SPR, and structure-activity relationships were determined.

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Three novel reduced pyrrolo [2,1-j] quinolines (cylindricines H, I and K) and one novel pyrido [2,1-j] quinoline ( cylindricine J) have been isolated from two further Tasmanian collections of the ascidian Clavelina cylindrica. These alkaloids are all related in structure to cylindricines A-G which have been obtained previously from the same ascidian. Cylindricines H-J are the first acetoxycylindricines obtained. Furthermore cylindricines I and J are isothiocyanates, the first such compounds identified from an ascidian, while cylindricine H is a thiocyanate which, together with cylindricines F and G, are the only ascidian thiocyanates known. Cylindricine K is an α,β -unsaturated ketone with the carbonyl group in the 8-position rather than the more usual 4-position as found in cylindricines A-G. Identification of the new alkaloids was by 1H n.m.r., 13C n.m.r., XHCORR, COSY and Fourier-transform i.r . Spectroscopy as well as high resolution e.i. mass spectrometry. Molecular modelling was used to assign relative stereochemistry. The geographical variation of the cylindricines is also reviewed.

Extracellular vesicles (EVs) are small membranous vesicles that contain an abundant cargo of different RNA species with specialized functions and clinical implications. Here, we introduce an updated online database (http://www.exoRBase.org), exoRBase 2.0, which is a repository of EV long RNAs (termed exLRs) derived from RNA-seq data analyses of diverse human body fluids. In exoRBase 2.0, the number of exLRs has increased to 19 643 messenger RNAs (mRNAs), 15 645 long non-coding RNAs (lncRNAs) and 79 084 circular RNAs (circRNAs) obtained from ∼1000 human blood, urine, cerebrospinal fluid (CSF) and bile samples. Importantly, exoRBase 2.0 not only integrates and compares exLR expression profiles but also visualizes the pathway-level functional changes and the heterogeneity of origins of circulating EVs in the context of different physiological and pathological conditions. Our database provides an attractive platform for the identification of novel exLR signatures from human biofluids that will aid in the discovery of new circulating biomarkers to improve disease diagnosis and therapy.

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