Biomedical subjects

Clemencia Pinilla

Publications and source records attributed to Clemencia Pinilla.

40 records · Page 3Linked to original sources

PubMed2002

Combinatorial peptide library-based identification of peptide ligands for tumor-reactive cytolytic T lymphocytes of unknown specificity.

A novel approach for the identification of tumor antigen-derived sequences recognized by CD8(+) cytolytic T lymphocytes (CTL) consists in using synthetic combinatorial peptide libraries. Here we have screened a library composed of 3.1 x 10(11) nonapeptides arranged in a positional scanning format, in a cytotoxicity assay, to search the antigen recognized by melanoma-reactive CTL of unknown specificity. The results of this analysis enabled the identification of several optimal peptide ligands, as most of the individual nonapeptides deduced from the primary screening were efficiently recognized by the CTL. The results of the library screening were also analyzed with a mathematical approach based on a model of independent and additive contribution of individual amino acids to antigen recognition. This biometrical data analysis enabled the retrieval, in public databases, of the native antigenic peptide SSX-2(41-49), whose sequence is highly homologous to the ones deduced from the library screening, among the ones with the highest stimulatory score. These results underline the high predictive value of positional scanning synthetic combinatorial peptide library analysis and encourage its use for the identification of CTL ligands.

Antigens, Neoplasm↗

PubMed2002

Targeting approaches to oral drug delivery.

Delivery of pharmaceuticals, particularly biotechnology products such as proteins, peptides, genes, oligonucleotides and vaccines, via the oral route remains problematic to this day. Instability in the gastrointestinal environment and poor permeability across the intestinal epithelial cell barrier contribute to poor oral bioavailability for many of these compounds. Current targeting strategies to overcome these issues are focused on three-part systems in which the drug (i) is loaded into a protective particulate carrier (ii) which is coated with target-specific ligands (iii) which mediate site-specific delivery of the drug-carrier complex. Protection from gastrointestinal degradative processes combined with site-specific delivery to absorptive regions of the intestinal tract is purported to yield high local concentrations of the drug of choice in close proximity with the epithelial cell layer and hence, transport across that barrier through a variety of mechanisms. This review examines the impact of cutting-edge technologies such as genomics and combinatorial chemistry on targeted oral drug delivery strategies. The explosion in rate of identification of new targets using genomics, together with high-throughput screening for target-specific ligands using combinatorial chemistry and phage display, has the potential to revolutionise this field. Particular reference is made to advances associated with targeted delivery of vaccines to M-cells or antigen-presenting cells in gut-associated lymphoid tissues.

Administration, Oral↗

PubMedDate not supplied

Towards a consensus on datasets and evaluation metrics for developing B-cell epitope prediction tools.

A B-cell epitope is the three-dimensional structure within an antigen that can be bound to the variable region of an antibody. The prediction of B-cell epitopes is highly desirable for various immunological applications, but has presented a set of unique challenges to the bioinformatics and immunology communities. Improving the accuracy of B-cell epitope prediction methods depends on a community consensus on the data and metrics utilized to develop and evaluate such tools. A workshop, sponsored by the National Institute of Allergy and Infectious Disease (NIAID), was recently held in Washington, DC to discuss the current state of the B-cell epitope prediction field. Many of the currently available tools were surveyed and a set of recommendations was devised to facilitate improvements in the currently existing tools and to expedite future tool development. An underlying theme of the recommendations put forth by the panel is increased collaboration among research groups. By developing common datasets, standardized data formats, and the means with which to consolidate information, we hope to greatly enhance the development of B-cell epitope prediction tools.

Animals↗

PubMedDate not supplied

Synthesis of platinum(II) chiral tetraamine coordination complexes.

The individual and combinatorial syntheses of individual as well as a mixture-based diversity of 195 112 platinum(II) coordination complexes of chiral tetraamines are described. The use of both solid-phase synthesis and solution phase follow-on approaches were found to best afford the title compounds.

Combinatorial Chemistry Techniques↗