The GAIIG sequence, common to the amyloid beta peptide (residues 29-33) and to the HIV-1 gp120 (residues 24-28 in a typical V3 loop), self-assembles into amyloid fibrils, as suggested by theory and the experiments presented here. The longer YATGAIIGNII sequence from the V3 loop also self-assembles into amyloid fibrils, of which the first three and the last two residues are outside the amyloid GAIIG core. We postulate that this sequence, with suitably selected modifications at the flexible positions, can serve as a designable scaffold for novel amyloid-based materials. Moreover, we report the single crystal X-ray structure of the beta-breaker peptide GAIPIG at 1.05 Å resolution. The structural information provided in this study could serve as the basis for structure-based design of potential inhibitors of amyloid formation.

The need to detect and monitor biomolecules, especially within cells, has led to the emerging growth of fluorescent probes. One of the most commonly used labeling techniques for this purpose is reversible metallochelate coupling via a nitrilotriacetic acid (NTA) moiety. In this study, we focus on the synthesis and characterization of three new porphyrin–NTA dyads, TPP-Lys-NTA, TPP-CC-Lys-NTA, and Py 3 P-Lys-NTA composed of a porphyrin derivative covalently connected with a modified nitrilotriacetic acid chelate ligand (NTA), for possible metallochelate coupling with Ni2+ ions and histidine sequences. Emission spectroscopy studies revealed that all of the probes are able to coordinate with Ni2+ ions and consequently can be applied as fluorophores in protein/peptide labeling applications. Using two different histidine-containing peptides as His6-tag mimic, we demonstrated that the porphyrin–NTA hybrids are able to coordinate efficiently with the peptides through the metallochelate coupling process. Moving one step forward, we examined the ability of these porphyrin–peptide complexes to penetrate and accumulate in cancer cells, exploring the potential utilization of our system as anticancer agents.

Cytotoxic potential of Ag(I) coordination compounds against cancer cells is widely recognized, but their frequently low water solubility and potential adverse interactions of Ag(I) ions in biological media require their...