Tetraantennary peptides [glycine(n)-NHCH(2)](4)C can form stable noncovalent structures by self-assembly through intermolecular hydrogen bonding. The oligopeptide chains assemble as polyglycine II to yield submicron-sized, flat, one-molecule-thick sheets. Attachment of alpha-N-acetylneuraminic acid (Neu5Acalpha) to the terminal glycine residues gives rise to water-soluble assembled glycopeptides that are able to bind influenza virus multivalently and inhibit adhesion of the virus to cells 10(3)-fold more effectively than a monomeric glycoside of Neu5Acalpha. Another antiviral strategy based on virus-promoted assembly of the glycopeptides was also demonstrated. Consequently, the self-assembly principle offers new perspectives on the design of multivalent antivirals.

Topotecan (TPT), a water-soluble derivative of camptothecin, is a potent antitumor poison of human DNA topoisomerase I (top1) that stabilizes the cleavage complex between the enzyme and DNA. The role of the recently discovered TPT affinity to DNA remains to be defined. The aim of this work is to clarify the molecular mechanisms of the TPT-DNA interaction and to propose the models of TPT-DNA complexes in solution in the absence of top1. It is shown that TPT molecules form dimers with a dimerization constant of (4.0 +/- 0.7) x 10(3) M(-1) and the presence of DNA provokes more than a 400-fold increase of the effective dimerization constant. Flow linear dichroism spectroscopy accompanied by circular dichroism, fluorescence, and surface-enhanced Raman scattering experiments provide evidence that TPT dimers are able to bind DNA by bridging different DNA molecules or distant DNA structural domains. This effect may provoke modification of the intrinsic geometry of the cruciform DNA structures, leading to the appearance of new crossover points that serve as the sites of the top1 loading position. The data presume the hypothesis of TPT-mediated modulation of top1-DNA recognition before ternary complex formation.

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The interactions of three bis‐netropsins (bis‐Nts), which are potent catalytic inhibitors of DNA‐binding enzymes, with three double‐stranded oligonucleotides (OLIGs), which contain sites of different specific affinities for each bis‐Nt, were analyzed. Raman spectroscopy was performed for selective monitoring of modifications of the bis‐Nt or the OLIG structure upon bis‐Nt–DNA binding, and surface‐enhanced Raman scattering spectroscopy (SERS) was an additional tool for topology studies of ligand–DNA complexes. The spectral data showed conformational changes of both partners (bis‐Nt and OLIG) upon complexation. Structural variations of bis‐Nts appeared to be dependent on a bis‐Nt–OLIG binding constant and were found to be small in the specific DNA binding and highest for nonspecific binding of bis‐Nt with the corresponding OLIG. The conformational changes of the OLIGs were varied with a bis‐Nt–OLIG binding constant in the same manner. The bis‐Nts seemed to induce a perturbation in the OLIG's structure, as well as in the positions of their direct binding. These DNA structural modification effects may explain the inhibition of DNA‐binding enzymes in the variety of very distinct DNA–enzyme binding sites by bis‐Nts reported previously. © 2000 John Wiley & Sons, Inc. Biopolymers (Biospectroscopy) 57: 272–281, 2000