Pepscan is a procedure for mapping and characterizing epitopes involving the synthesis of overlapping peptides and analysis of the peptides in enzyme-linked immunosorbent assays . The method is based on combinatorial chemistry and was pioneered by Mario Geysen and coworkers. Wikipedia.
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Advances in Immunology | Year: 2012
Although vaccines have proven life saving against a myriad of infectious diseases, various pathogens have remained refractory to prophylaxis of their host by active immunization. New insights in the three dimensional (3D) structure, domain organization and dynamics of viral and bacterial surface proteins can guide the design of effective vaccines in several ways. In this review we highlight recent developments in structure-based vaccine design that are aimed at stabilization of native conformations and focusing immune response to conserved epitopes. Detailed 3D structures of pathogen surface proteins provide knowledge on how to minimize complex antigens or how to redesign the surface of an immunogen in order to induce only relevant neutralizing antibodies against a broad range of serotypes. Structure - based vaccines with reduced complexity and broad efficacy could greatly enhance the number of people that might benefit from the therapies that are developed. © 2012 Elsevier Inc. Source
Pepscan | Date: 2014-03-07
The disclosure relates to the field of candidate drug testing and drug development. Described are methods for providing a compound composed of at least one molecule attached via at least two linkages to a molecular scaffold, the method comprising providing a scaffold comprising at least a first and a second reactive group; providing at least one molecule able to react with the at least first and second reactive group; and contacting the scaffold with at least one molecule to form at least two linkages between the scaffold and the molecule in a coupling reaction, wherein the formation of a linkage accelerates the formation of a consecutive linkage. The coupling reaction may be performed in solution, such as an aqueous solution. Furthermore, described is a method for selecting a candidate drug compound comprising providing a library of the compounds and determining the binding of a target molecule to the compounds.
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.4.5-3 | Award Amount: 3.90M | Year: 2008
The balance between bone resorption and bone formation determines the mass and structural integrity of the skeleton and is disturbed in osteoporosis. In contrast to the molecular mechanisms regulating bone resorption, knowledge of the mechanisms regulating bone formation is limited. A recent breakthrough has been the identification of a link between bone mass in humans with rare bone disorders and gain- or loss-of function mutations of the Wnt co-receptor LRP5 or the Wnt antagonist sclerostin. The mechanism, however, underlying these actions on Wnt signalling is unclear. We propose studies with the following specific aims: i) to characterize the clinical, bioschemical, radiological and histological features of patients with sclerosteosis, van Buchem disease and other craniotubular hyperostoses ii) to determine the genetic defect in patients with craniotubular hyperostoses and establish putative genotype-phenotype correlations iii) to unravel the molecular mechanism of the inhibitory action of sclerostin on bone formation and to determine how genetic variations in SOST, LRP5 and Wnt signalling pathway modify bone architecture and remodelling iv) to reveal the pattern of sclerostin expression by analysis of the SOST promoter and by histomorphometry of human bone biopsies v) to identify and characterize co-factors of the LRP5 signalling and their in vivo actions in relevant animal models vi) to identify epitopes in sclerostin that mediate the interaction with LRP5, raise peptide-bound protein mimics and test them in vitro and in animal models of bone loss. These studies will not only help understanding the molecular basis of critical signalling pathway in bone formation but will also provide insight into normal and disturbed modulation of bone remodelling. Moreover, they will help in the design of bone forming interventions for the treatment of patients with osteoporosis.
Pepscan | Date: 2014-03-07
The disclosure relates to the field of candidate drug testing and drug development. A method is provided for providing a compound composed of at least one molecule attached via at least two linkages to a molecular scaffold, the method comprising providing a scaffold comprising at least a first and a second reactive group; providing at least one molecule capable of reacting with the at least first and second reactive group; contacting the scaffold with at least one molecule to form at least two linkages between the scaffold and the at least one molecule in a coupling reaction, wherein the formation of a linkage accelerates the formation of a consecutive linkage, preferably wherein the coupling reaction is performed in solution, more preferably in an aqueous solution. Furthermore, a method is provided for selecting a candidate drug compound comprising providing a library of compounds hereof and determining the binding of a target molecule to the compounds.
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-03-2015 | Award Amount: 6.00M | Year: 2016
We hypothesize that inappropriate thyroid hormone action in target cells is a common mechanism underlying susceptibility to age-related degenerative diseases and co-morbidities. Although regulation of systemic thyroid status is well understood and underpins treatment of common thyroid disease, it is only in the last decade that the importance of local regulation of thyroid hormone action in tissue development, homeostasis and repair has been identified. During evolution, this complex temporal and cell-specific regulation has been optimized for development and reproductive fitness but NOT for ageing. Humans with their exceptional longevity are thus exposed to a prolonged period of suboptimal local thyroid hormone action. Consistent with this, thyroid status is a continuous variable within the population that is related to fracture risk, muscle mass and cognitive decline. Moreover, in healthy longevity thyroid status is characterized by thyroid stimulating hormone in the upper half of the reference range. In these studies, we will determine how local regulation of thyroid hormone action controls tissue homeostasis and repair, whilst its dysregulation is a common mechanism underlying chronic disease development during ageing. We focus on osteoporosis, osteoarthritis, neurodegeneration and sarcopenia as paradigm age-related, degenerative disorders. Using cutting-edge technology, we will (i) identify thyroid hormone dependent biomarkers for disease susceptibility in bone, cartilage, central nervous system and skeletal muscle, (ii) manipulate cell-specific thyroid hormone action in these tissues and (iii) develop cell-type specific modulators of thyroid hormone action. THYRAGE integrates cross-disciplinary expertise from clinical and basic scientists, endocrinologists, neuroscientists, gerontologists, and industry-based peptide scientists. These studies will identify and validate novel strategies for prevention and treatment of chronic age-related degenerative disease.