Lanthanide complexes as fluorescent indicators for neutral sugars and cancer biomarkers

Simple water soluble lanthanum and europium complexes are effective at detecting neutral sugars as well as glyco- and phospholipids. In solutions at physiologically relevant pH the fluorescent lanthanum complex binds neutral sugars with apparent binding constants comparable to those of arylboronic acids. Interference from commonly occurring anions is minimal. The europium complex detects sialic acid-containing gangliosides at pH 7.0 over an asialoganglioside. This selectivity is attributed, in large part, to the cooperative complexation of the oligosaccharide and sialic acid residues to the metal center, based on analogous prior studies. In MeOH, lysophosphatidic acid (LPA), a biomarker for several pathological conditions including ovarian cancer, is selectively detected by the europium complex. LPA is also detected via a fluorescence increase in human plasma samples. The 2-sn-OH moiety of LPA plays a key role in promoting binding to the metal center. Other molecules found in common brain ganglioside and phospholipid extracts do not interfere in the ganglioside or LPA fluorescence assays

JigCell: A New Environment to Simulate the Dynamics of Memory Formation

Since their initial discovery, long-term potentiation (LTP), and long-term depression (LTD) are accepted as the main biomolecular mechanism that controls memory acquisition. In doing this, both mechanisms are fairly complex and involve specific triggers and many cascades reactions that cross-talk and communicate with others. Thus, they are very complex. To reveal how these mechanisms operate and instruct the brain to remember and forget, one judicious approach is developing the mathematical models of processes. However, this notion requires some basic knowledge regarding ordinary differential equations and writing codes. To this respect, it can be postulated that tools, which can be utilized rather by everyone, would certainly expedite and facilitate the formulation of such models. With this rationale in mind, we demonstrate that JigCell offers the perfect platform to develop such models of LTP. Our choice for this tool stems from the fact that it is designed to simulate complex biological systems in a modular way. Thus, this manuscript is crafted to illustrate how this model was constructed in the JigCell environment and to give an idea of how this tool works

The Synthesis of Peptide-Conjugated Poly(2-Ethyl-2-Oxazoline)-bpoly(L-Lactide) (PEtOx-B-PLA) Polymeric Systems Through the Combination of Controlled Polymerization Techniques and Click Reactions

To optimize the therapeutic effect of pharmaceutical agents, drug delivery systems tailored from FDA-approved polymers like poly(L-lactide) (PLA) is an effective strategy. Because of their hydrophobic character, these systems greatly suffer from reduced circulation time thus, amphiphilic block copolymers became favourable to overcome this limitation. Of them, poly(oxazoline)-b-poly(L-lactide) are of choice as poly(oxazoline) (PEtOx) is compatibile, biodegradable, while exhibiting minimum cytotoxicity. To tailor selective drug targeting drug delivery systems, whereby their selectivity for tumour tissues is maximised, these polymers should be decorated with so-called tumour-homing agents, such as antibodies, peptides and so forth. To this respect, we designed a new block copolymer, allyl-poly(2-ethyl-2-oxazoline)-b-poly(L-lactide) allyl-(PEtOx-b-PLA) and its subsequent conjugation to tumour-homing peptides, peptide-18 and peptide-563 at the terminal position. In this manuscript, we report our synthetic route to obtain this building block and its conjugation to tumour-homing agents

Macrocycle-derived functional xanthenes and progress towards concurrent detection of glucose and fructose

The detection of saccharides in biological media is of great current importance for the monitoring of disease states. We have previously reported that solutions of boronic acid-functionalized macrocycles form acyclic oligomeric materials in situ. The oligomers contain fluorescent xanthene moieties. Current efforts are aimed at modulating the spectroscopic responses of these materials for the analysis of specific sugars. We describe conditions whereby the xanthene boronic acids exhibit high colorimetric fructose selectivity. In contrast, at physiological levels selective glucose monitoring can be achieved via fluorescence. Additionally, we describe a method which exhibits promise for detecting both glucose and fructose at dual wavelengths in the UV-Vis region. Mechanistic rationale for each of these findings is presented