Medicinal Chemistry Unit
Medicinal Chemistry Unit
Kaushik A.,Medicinal Chemistry Unit
Current Chemical Biology | Year: 2014
Snake toxins consist of different pharmacologically lively peptides and proteins. These hemorrhagic proteins are metalloproteinases with molecular weights between 20 to 100 kDa. SVMPs are zinc-dependent types and with a multidomain association. SVMPs consist of only the proteinase type of domain, while some contain other types such as cysteine, lectin and disintegrins. They are analogous with both MMP and ADAMs group. SVMPs are 30% of the total protein of snake’s venoms. Hemorrhagic activity and the stimulation of local and systemic bleeding generally are due to SVMPs. Necrosis, skin damage, inflammatory reaction, arthritis and are responsible for causing paralysis. These proteinase types also hold diverse functions such as the disruption of hemostasis, platelet aggregation and pro-inflammatory activities. This short review focuses on the most prominent effects induced by SVMPs. © 2014 Bentham Science Publishers.
Deacon S.P.E.,Center for Polymer Therapeutics |
Apostolovic B.,Ecole Polytechnique Federale de Lausanne |
Carbajo R.J.,Medicinal Chemistry Unit |
Schott A.-K.,Medicinal Chemistry Unit |
And 5 more authors.
Biomacromolecules | Year: 2011
Polymer therapeutics, including polymeric drugs and polymer-protein conjugates, are clinically established as first-generation nanomedicines. Knowing that the coiled-coil peptide motif is fundamentally important in the regulation of many cellular and pathological processes, the aim of these studies was to examine the feasibility of designing polymer conjugates containing the coiled-coil motif as a putative therapeutic "molecular switch". To establish proof of concept, we prepared a mPEG-FosWC conjugate by reacting mPEG-maleimide (Mw 5522 g mol-1, M w/Mn 1.1) with a FosW peptide synthesized to contain a terminal cysteine residue (FosWC). Its ability to form a stable coil-coil heterodimer with the target c-Jun sequence of the oncogenic AP-1 transcription factor was investigated using 2D 15N-HSQC NMR together with a recombinantly prepared 15N-labeled c-Jun peptide ([ 15N]r-c-Jun). Observation that heterodimerization was achieved and that the polymer did not sterically disadvantage hybridization suggests an important future for this new family of polymer therapeutics. © 2010 American Chemical Society.
Delgado A.,Medicinal Chemistry Unit |
Martiez-Cartro M.,Medicinal Chemistry Unit
Current Medicinal Chemistry | Year: 2016
It is accepted that sphingolipids (SL) are not only structural lipids in cellular membranes, but also key regulators of different cell process. Sphingosine-1-phosphate (S1P) is a member of this family involved, inter alia, in cell migration, angiogenesis and cell proliferation processes, being able to play different intracellular and extracellular roles. When S1P is transported out of the cell, it binds S1P specific G protein-coupled receptors, which are mainly involved in the regulation of the immune, vascular and nervous systems. These effects account for the vast diversity of functions that arise from the activation of S1P receptors. Deregulation of S1P levels is correlated with several pathologies, such as autoimmune disorders and cancer. Consequently, the correct modulation of these receptors represents a valuable approach for the development of new therapeutic strategies. Along this line, the non-selective S1P receptor agonist fingolimod (FTY720) has been commercialized recently for the treatment of multiple sclerosis and several related S1P receptor modulators are ongoing clinical trials. However, despite the progress in this field, the biological functions of S1P receptors are not still well elucidated. For this reason, several studies are being developed in order to better understand the functions of these receptors, making use of new selective S1P receptor agonists and antagonists as pharmacological tools. © 2016 Bentham Science Publishers.