1,721,237 research outputs found
Estratto di vna Lettera di risposta alla precedente, scritta dal Sig. Dr. Alessandro Pini à Iacopo Grandi dal Golfo di Corone li 15 Nouembre 1685. con alcune annotazioni del medesimo Grandi. In: Jacopo Grandi, Risposta di Iacopo Grandi Medico Professore d
No full textDedication:Pagination: 136-155Volumes: 1Text Genre:Letter
ANTICORPI E PEPTIDI -I farmaci del XXI secolo-
No full textLibro di testo per studenti di Biotecnologi
Phage display of antibody fragments
No full textIn recent years, phage display of peptides and proteins has become a very popular method in oncology, immunology, protein engineering and ligand-receptor studies among others. Antibody fragments, as Fabs or single chain Fv, have been among the first proteins to be displayed on the surface of a filamentous bacteriophage with a procedure initially described in 1990 by McCafferty et al. (Nature, 348, 552-554). From that time, molecular biology techniques have allowed the creation of large repertoires of antibody fragments from antibody V genes, bypassing hybrydoma technology and even immunisation. A large number of phage antibody libraries, from which molecules of the desired functional properties can be rapidly selected, have been built and distributed in many laboratories world-wide. Antibody fragments recovered from phage libraries generally show moderate binding strength; with different systems of biopanning binders can be obtained with dissociation constant ranged between 10-(5) to 10-(8) M. Nevertheless, antibody fragments can be furtherly modified to improve affinity or avidity, respectively by mutating crucial residues of complementarity determining regions or by increasing the number of binding sites making dimeric, trimeric or multimeric molecules. Here, we summarise the latest progress in this field, with particular reference to applications of scFv in the diagnosis and therapy of solid tumours and in the molecular mimicry of viral antigens and membrane receptors. In fact, the production of artificial protein epitopes by phage antibodies is becoming a valid system to overcome problems caused by difficult cloning and low expression of particular recombinant protein
COMPOSTI ANTI TNF-ALPHA E LORO USI
No full textLa presente invenzione riguarda un peptide, i suoi derivati multimerici, relativa composizione farmaceutica e loro usi in terapia, in particolare per inibire l’attività del TNF-alpha
Analytical and numerical investigation of the heat exchange effect on the dynamic behaviour of natural circulation with internally heated fluids
No full textIn this paper, the study of the heat exchange effect on the dynamic behaviour of single-phase natural circulation with internal heat generation is presented. In order to predict natural circulation instabilities, two different methods of analysis are developed and compared. The first approach is a linear analysis in which the governing equations are firstly linearized around a steady-state solution of the system and then treated by means of the Fourier transform. This strategy is adopted to compute, in a semi-analytical way, dimensionless stability maps for different system configurations, highlighting the heat exchange effect on the system dynamics. The second approach consists in numerically solving the nonlinear governing equations and allows investigating some transients of interest. For this purpose, an object-oriented one-dimensional model of natural circulation loops has been developed, and the corresponding results have been compared with RELAP5 and Computational Fluid-Dynamics (CFD) time-dependent simulations. The developed models have been applied to investigate the dynamic behaviour of two loop configurations characterized by large instability regions, namely the Horizontal Heater-Horizontal Cooler (HHHC) and the Vertical Heater-Horizontal Cooler (VHHC)
The influence of the wall thermal inertia over a single-phase natural convection loop with internally heated fluids
No full textThis paper deals with the influence of the piping material thermal and geometrical properties on the dynamic stability of single-phase natural circulation loops. To this purpose, a semi-analytical approach is developed by adopting the tools provided by the linear analysis. By considering a generic natural circulation loop configuration with a localized heat flux and a homogenously distributed Internal Heat Generation (IHG), the governing equations (mass, momentum and energy balance) are linearized around a steady-state solution of the system and treated by means of the Fourier transform to obtain dimensionless stability maps. Moreover, in order to verify the linear analysis methodology, a numerical strategy is adopted to solve the nonlinear governing equations and to investigate the natural circulation dynamics in the time domain. In principle, both the developed approaches can be applied to any natural circulation loop configuration. In the present work, the linear and the nonlinear analyses are applied to a specific natural circulation loop geometry, namely the Horizontal Heater Horizontal Cooler (HHHC) one. In this regard, an Object-Oriented (O-O) one-dimensional model of the HHHC loop is developed. For the assessment of the O-O model, the obtained results are compared with RELAP5 and Computational-Fluid-Dynamics (CFD) time-dependent simulations
Phage display and colony filter screening for high-throughput selection of antibody libraries
No full textDuring the last 12 years, antibody combinatorial libraries have provided a new approach for the construction and production of reagents and drugs based on the human monoclonal antibodies. Studies employing antibodies or antibody mimics have become an important part of the explosive growth of proteomics. This places tremendous emphasis on the new approaches for faster library screening, improved methods of selection and evaluation of novel applications. The phage display system, together with its variants of ribosome and bacterial display, is the most extensively used method for the rapid screening of large antibody libraries. However, in the last two years the need to improve selection methods together with a complex patent situation regarding the phage display system, has also directed research towards the possibility of performing antibody selection by colony filter screening. Here, we summarise the results obtained by these different methods of selection comparing their efficacy and advantage
Antimicrobial peptide, branched forms thereof, and their use in the treatment of bacterial infections
Full text linkThe instant invention refers to an antibacterial peptide with all aminoacids in D-configuration, possessing strong
antimicrobial activity against Gram-negative and Gram-positive bacteria and Candida strains. The peptide can be in linear form or
multimerised on a skeleton of polyacrylamide, of dextrane units or on a skeleton of ethylene glycol units. The peptide is resistant
to proteolysis especially when synthesized in the tetra-branched form where identical peptide sequences are linked together by an
appropriate molecular scaffold
Branched peptides as therapeutics
No full textThe concept of ‘magic bullet’, initially ascribed to immunoglobulins by Paul Ehrlich at the beginning of the
20th century and strengthened by the hybridoma technology of Kohler and Milstein in the mid 70s, can nowadays be attributed
to different target-specific molecules, such as peptides. This attribution is increasingly valid in light of the explosion
of new technologies for peptide library construction and screening, not to mention improvements in peptide synthesis
and conjugation and in-vivo peptide stability, which make peptide molecules specific bullets for targeting pathological
markers and pathogens. Today, hundreds of peptides are being developed and dozens are in clinical trials for a variety of
diseases, demonstrating that the general reluctance towards peptide drugs that existed a decade ago has now been overcome.
In spite of this progress, the development of new peptide drugs has largely been limited by their short half-life.
Branched peptides such as Multiple Antigen Peptides (MAPs) were invented in the 80s by Tam [Tam, J.P., (1998) Proc.
Natl. Acad. Sci. USA, 85, 5409] and have been extensively tested to reproduce single epitopes to stimulate the immune
system for new vaccine discovery. In our lab we discovered that MAP molecules acquire strong resistance to proteases
and peptidases. This resistance renders MAPs very stable and thus suitable for drug development. Here we report our experience
with several MAP molecules in different biotechnological applications ranging from antimicrobial and anti toxin
peptides to peptides for tumor targeting
Oligo-branched peptides for tumor targeting: From magic bullets to magic forks
No full textBACKGROUND: Selective targeting of tumor cells is the final goal of research and drug discovery for cancer diagnosis, imaging and therapy. After the invention of hybridoma technology, the concept of magic bullet was introduced into the field of oncology, referring to selective killing of tumor cells, by specific antibodies. More recently, small molecules and peptides have also been proposed as selective targeting agents.
OBJECTIVE/METHODS: We analyze the state of the art of tumor-selective agents that are presently available and tested in clinical settings. A novel approach based on 'armed' oligo-branched peptides as tumor targeting agents, is discussed and compared with existing tumor-selective therapies mediated by antibodies, small molecules or monomeric peptides.
RESULTS/CONCLUSIONS: Oligo-branched peptides could be novel drugs that combine the advantages of antibodies and small molecules
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