Nuclear Magnetic Resonance Spectroscopy: A Multifaceted Toolbox to Probe Structure, Dynamics, Interactions, and Real-Time Release Kinetics in Peptide-Liposome Formulations.

Liposomal formulations represent attractive biocompatible and tunable drug delivery systems for peptide drugs. Among the tools to analyze their physicochemical properties, nuclear magnetic resonance (NMR) spectroscopy, despite being an obligatory technique to characterize molecular structure and dynamics in chemistry as well as in structural biology, yet appears to be rather sparsely used to study drug-liposome formulations. In this work, we exploited several facets of liquid-state NMR spectroscopy to characterize liposomal delivery systems for the apelin-derived K14P peptide and K14P modified by Nα-fatty acylation.

Glacial Steady State Topography Controlled by the Coupled Influence of Tectonics and Climate.

Glaciers and rivers are the main agents of mountain erosion. While in the fluvial realm empirical relationships and their mathematical description, such as the stream power law, improved the understanding of fundamental controls on landscape evolution, simple constraints on glacial topography and governing scaling relations are widely lacking. We present a steady state solution for longitudinal profiles along eroding glaciers in a coupled system that includes tectonics and climate.

Arsenic Speciation in Mekong Delta Sediments Depends on Their Depositional Environment.

Arsenic contamination in groundwater is pervasive throughout deltaic regions of Southeast Asia and threatens the health of millions. The speciation of As in sediments overlying contaminated aquifers is poorly constrained. Here, we investigate the chemical and mineralogical compositions of sediment cores collected from the Mekong Delta in Vietnam, elucidate the speciation of iron and arsenic, and relate them to the sediment depositional environment.

New Insights in Thrombin Inhibition Structure-Activity Relationships by Characterization of Octadecasaccharides from Low Molecular Weight Heparin.

Low Molecular Weight Heparins (LMWH) are complex anticoagulant drugs that mainly inhibit the blood coagulation cascade through indirect interaction with antithrombin. While inhibition of the factor Xa is well described, little is known about the polysaccharide structure inhibiting thrombin. In fact, a minimal chain length of 18 saccharides units, including an antithrombin (AT) binding pentasaccharide, is mandatory to form the active ternary complex for LMWH obtained by alkaline β-elimination (e.

Northward migration of the eastern Himalayan syntaxis revealed by OSL thermochronometry.

Erosion influences the dynamical evolution of mountains. However, evidence for the impact of surface processes on tectonics mostly relies on the circumstantial coincidence of rugged topography, high stream power, erosion, and rock uplift. Using the optically stimulated luminescence (OSL) thermochronometry technique, we quantified the spatial and temporal exhumation of the eastern Himalayan syntaxis.

Analytical comparison of a US generic enoxaparin with the originator product: The focus on comparative assessment of antithrombin-binding components.

Enoxaparin sodium, a low-molecular-weight heparin (LMWH) prepared from porcine intestinal heparin, is widely used for the prevention and treatment of venous thromboembolism. The antithrombotic activity of heparin is mediated mainly through its activation of antithrombin (AT) and subsequent inhibition of coagulation factors. Heparin is a complex heteropolymer and the sulfation pattern of its alternating uronic acid and glucosamine sugar units is a major factor influencing its biological activity.

Erosion by an Alpine glacier.

Assessing the impact of glaciation on Earth's surface requires understanding glacial erosion processes. Developing erosion theories is challenging because of the complex nature of the erosion processes and the difficulty of examining the ice/bedrock interface of contemporary glaciers. We demonstrate that the glacial erosion rate is proportional to the ice-sliding velocity squared, by quantifying spatial variations in ice-sliding velocity and the erosion rate of a fast-flowing Alpine glacier.

Analytical and statistical comparability of generic enoxaparins from the US market with the originator product.

Low-molecular-weight heparins (LMWHs) are complex anticoagulant drugs, made from heparin porcine mucosa starting material. Enoxaparin sodium manufactured by Sanofi is one of the most widely prescribed LMWHs and has been used since 1993 in the USA. In 2010, US Food and Drug Administration approval for supplying generic enoxaparin was granted to Sandoz and subsequently to Amphastar.

Isolation of a pure octadecasaccharide with antithrombin activity from an ultra-low-molecular-weight heparin.

Heparin and low-molecular-weight heparins (LMWHs) are anticoagulant drugs that mainly inhibit the coagulation cascade by indirectly interacting with factor Xa and factor IIa (thrombin). Inhibition of factor Xa by antithrombin (AT) requires the activation of AT by specific pentasaccharide sequences containing 3-O-sulfated glucosamine. Activated AT also inhibits thrombin by forming a stable ternary complex of AT, thrombin, and a polysaccharide (requires at least an 18-mer/octadeca-mer polysaccharide).

Worldwide acceleration of mountain erosion under a cooling climate.

Climate influences the erosion processes acting at the Earth's surface. However, the effect of cooling during the Late Cenozoic era, including the onset of Pliocene-Pleistocene Northern Hemisphere glaciation (about two to three million years ago), on global erosion rates remains unclear. The uncertainty arises mainly from a lack of consensus on the use of the sedimentary record as a proxy for erosion and the difficulty of isolating the respective contributions of tectonics and climate to erosion.

Heparin dodecasaccharide containing two antithrombin-binding pentasaccharides: structural features and biological properties.

The antithrombin (AT) binding properties of heparin and low molecular weight heparins are strongly associated to the presence of the pentasaccharide sequence AGA*IA (A(NAc,6S)-GlcUA-A(NS,3,6S)-I(2S)-A(NS,6S)). By using the highly chemoselective depolymerization to prepare new ultra low molecular weight heparin and coupling it with the original separation techniques, it was possible to isolate a polysaccharide with a biosynthetically unexpected structure and excellent antithrombotic properties. It consisted of a dodecasaccharide containing an unsaturated uronate unit at the nonreducing end and two contiguous AT-binding sequences separated by a nonsulfated iduronate residue.

Ultra-low-molecular-weight heparins: precise structural features impacting specific anticoagulant activities.

Ultra-low-molecular-weight heparins (ULMWHs) with better efficacy and safety ratios are under development; however, there are few structural data available. The main structural features and molecular weight of ULMWHs were studied and compared to enoxaparin. Their monosaccharide composition and average molecular weights were determined and preparations studied by nuclear magnetic resonance spectroscopy, scanning ultraviolet spectroscopy, circular dichroism and gel permeation chromatography.

Heparin sodium compliance to USP monograph: structural elucidation of an atypical 2.18 ppm NMR signal.

The ¹H nuclear magnetic resonance (NMR) acceptance criteria in the new heparin US Pharmacopeia (USP) monograph do not take into account potential structural modifications responsible for any extra signals observed in ¹H NMR spectra, some purified heparins may be non-compliant under the proposed new USP guidelines and incorrectly classified as unsuitable for pharmaceutical use. Heparins from the "ES" source, containing an extra signal at 2.18 ppm, were depolymerized under controlled conditions using heparinases I, II, and III.

Effects on molecular conformation and anticoagulant activities of 1,6-anhydrosugars at the reducing terminal of antithrombin-binding octasaccharides isolated from low-molecular-weight heparin enoxaparin.

Terminal 1,6-anhydro-aminosugars (1,6-anAS) are typical structural moieties of enoxaparin, a low-molecular-weight heparin (LMWH) widely used for prevention and treatment of thrombotic disorders. In the enoxaparin manufacturing process, these modified amino sugars are formed during the β-eliminative cleavage of heparin. To investigate the effect of terminal anAS on antithrombin (AT) binding and on inhibition of factor Xa (FXa), two octasaccharides containing modified AT-binding pentasaccharide sequences were isolated from enoxaparin.

Heparin sodium compliance to the new proposed USP monograph: elucidation of a minor structural modification responsible for a process dependent 2.10 ppm NMR signal.

Heparin is a highly sulfated hetero polysaccharide mixture found and extracted from mammalian tissues. It has been widely used as an anticoagulant drug during the past decades. In the new proposed USP heparin monograph, the ¹H NMR acceptance criteria to prevent contamination by over sulfated chondroitin sulfate (OSCS), or other persulfated glycosaminoglycans, specifies that no unidentified signals greater than 4% of the mean of signal height of 1 and 2 should be present in the following ranges: 0.