Search results for "MIME"

Development of Novel Peptide-Based Michael Acceptors Targeting Rhodesain and Falcipain-2 for the Treatment of Neglected Tropical Diseases (NTDs)

2017

This paper describes the development of a class of peptide-based inhibitors as novel antitrypanosomal and antimalarial agents. The inhibitors are based on a characteristic peptide sequence for the inhibition of the cysteine proteases rhodesain of Trypanosoma brucei rhodesiense and falcipain-2 of Plasmodium falciparum. We exploited the reactivity of novel unsaturated electrophilic functions such as vinyl-sulfones, -ketones, -esters, and -nitriles. The Michael acceptors inhibited both rhodesain and falcipain-2, at nanomolar and micromolar levels, respectively. In particular, the vinyl ketone 3b has emerged as a potent rhodesain inhibitor (k2nd = 67 × 106 M-1 min-1), endowed with a picomolar b…

Mixed topological semimetals driven by orbital complexity in two-dimensional ferromagnets

2018

The concepts of Weyl fermions and topological semimetals emerging in three-dimensional momentum space are extensively explored owing to the vast variety of exotic properties that they give rise to. On the other hand, very little is known about semimetallic states emerging in two-dimensional magnetic materials, which present the foundation for both present and future information technology. Here, we demonstrate that including the magnetization direction into the topological analysis allows for a natural classification of topological semimetallic states that manifest in two-dimensional ferromagnets as a result of the interplay between spin-orbit and exchange interactions. We explore the emerg…

Photoactivatable Adhesive Ligands for Light-Guided Neuronal Growth

2018

Neuro-regeneration after trauma requires growth and reconnection of neurons to reestablish information flow in particular directions across the damaged tissue. To support this process, biomaterials for nerve tissue regeneration need to provide spatial information to adhesion receptors on the cell membrane and to provide directionality to growing neurites. Here, photoactivatable adhesive peptides based on the CASIKVAVSADR laminin peptidomimetic are presented and applied to spatiotemporal control of neuronal growth to biomaterials in vitro. The introduction of a photoremovable group [6-nitroveratryl (NVOC), 3-(4,5-dimethoxy-2-nitrophenyl)butan-2-yl (DMNPB), or 2,2′-((3′-(1-hydroxypropan-2-yl)…

Structural commonalities and deviations in the hierarchical organization of crossed-lamellar shells: A case study on the shell of the bivalve Glycyme…

2016

11 pages; International audience; The structural organization of the palliostracum—the dominant part of the shell which is formed by the mantle cells—of Glycymeris glycymeris (Linné 1758) is comprised of five hierarchical levels with pronounced structural commonalities and deviations from other crossed-lamellar shells. The hierarchical level known as second order lamellae, present within other crossed-lamellar shells, is absent highlighting a short-coming of the currently used nomenclature. On the mesoscale, secondary microtubules penetrate the palliostracum and serve as crack arrestors. Moreover, the growth lamellae follow bent trajectories possibly impacting crack propagation, crack defle…

In Situ, Light-Guided Axon Growth on Biomaterials via Photoactivatable Laminin Peptidomimetic IK(HANBP)VAV

2018

The ability to guide the growth of neurites is relevant for reconstructing neural networks and for nerve tissue regeneration. Here, a biofunctional hydrogel that allows light-based directional control of axon growth in situ is presented. The gel is covalently modified with a photoactivatable derivative of the short laminin peptidomimetic IKVAV. This adhesive peptide contains the photoremovable group 2-(4′-amino-4-nitro-[1,1′-biphenyl]-3-yl)propan-1-ol (HANBP) on the Lys rest that inhibits its activity. The modified peptide is highly soluble in water and can be simply conjugated to -COOH containing hydrogels via its terminal -NH 2 group. Light exposure allows presentation of the IKVAV adhesi…

PPARδ Modulation by GW501516: An Unsuccessful Exercise Mimetic.

2017

Development of a New Antileishmanial Aziridine-2,3-Dicarboxylate-Based Inhibitor with High Selectivity for Parasite Cysteine Proteases

2015

ABSTRACT Leishmaniasis is one of the major neglected tropical diseases of the world. Druggable targets are the parasite cysteine proteases (CPs) of clan CA, family C1 (CAC1). In previous studies, we identified two peptidomimetic compounds, the aziridine-2,3-dicarboxylate compounds 13b and 13e, in a series of inhibitors of the cathepsin L (CL) subfamily of the papain clan CAC1. Both displayed antileishmanial activity in vitro while not showing cytotoxicity against host cells. In further investigations, the mode of action was characterized in Leishmania major . It was demonstrated that aziridines 13b and 13e mainly inhibited the parasitic cathepsin B (CB)-like CPC enzyme and, additionally, ma…

A new twist on sea silk : the peculiar protein ultrastructure of fan shell and pearl oyster byssus

2018

11 pages; International audience; Numerous mussel species produce byssal threads - tough proteinaceous fibers, which anchor mussels in aquatic habitats. Byssal threads from Mytilus species, which are comprised of modified collagen proteins - have become a veritable archetype for bio-inspired polymers due to their self-healing properties. However, threads from different species are comparatively much less understood. In particular, the byssus of Pinna nobilis comprises thousands of fine fibers utilized by humans for millennia to fashion lightweight golden fabrics known as sea silk. P. nobilis is very different from Mytilus from an ecological, morphological and evolutionary point of view and …

Development of novel 1,4-benzodiazepine-based Michael acceptors as antitrypanosomal agents

2016

Novel 1,4-benzodiazepines, endowed with a Michael acceptor moiety, were designed taking advantage of a computational prediction of their pharmacokinetic parameters. Among all the synthesized derivatives, we identified a new lead compound (i.e., 4a), bearing a vinyl ketone warhead and endowed with a promising antitrypanosomal activity against Trypanosoma brucei brucei (IC50 = 5.29 µM), coupled with a lack of cytotoxicity towards mammalian cells (TC50>100 µM).

Hierarchical architecture of sponge spicules: biocatalytic and structure-directing activity of silicatein proteins as model for bioinspired applicati…

2016

Since the first description of the silicateins, a group of enzymes that mediate the formation of the amorphous, hydrated biosilica of the skeleton of the siliceous sponges, much progress has been achieved in the understanding of this biomineralization process. These discoveries include, beside the proof of the enzymatic nature of the sponge biosilica formation, the dual property of the enzyme, to act both as a structure-forming and structure-guiding protein, and the demonstration that the initial product of silicatein is a soft, gel-like material that has to undergo a maturation process during which it achieves its favorable physical-chemical properties allowing the development of various t…