Induction of cytotoxic T-cell-mediated virus-clearing responses by influenza virus T cell determinant-con-

Oligonucleotide-peptide hybrids have potential for use as antisense inhibitors of gene expression, with the peptide helping to increase the intracellular concentration of the active oligonucleotide. The preparation of such hybrids can be achieved by the coupling of thiol-derivatized oligonucleotides with maleimido-peptides. We have developed reliable methods for preparing 5'-thiol oligonucleotides in good yields using phosphoramidite chemistry and coupling 6-(tritylthio)hexyl phosphoramidite as the 5'-terminal residue. The use of highly pure thiol phosphoramidite as well as a manual iodine treatment after this coupling were found to be important. Oligonucleotide-peptide hybrids were prepared in high yield (85%) by reacting freshly purified 5'-thiol oligonucleotides with peptides derivatized at their N-terminus with a maleimido functionality.

Clinical and immunologic responses to a B-cell epitope vaccine in HER2/neuoverexpressing advanced gastric cancer patients -results from Phase 1b trial IMU.ACS.

An optimised method of solution cyclisation gave us access to a series of peptides including SLKIDNLD (2). We investigated the crystallographic complexes of the HIV integrase (HIV-IN) catalytic core domain with 13 of the peptides and identified multiple interactions at the binding site, including hydrogen bonds with residues Thr125 and Gln95, that have not previously been described as being accessible within the binding site. We show that the peptides inhibit the interaction of lens epithelium-derived growth factor (LEDGF) with HIV-IN in a proximity AlphaScreen assay and in an assay for the LEDGF enhancement of HIV-IN strand transfer. The interactions identified represent a potential framework for the development of new HIV-IN inhibitors.