The alteration of amino acid register in peptides could affect their folding properties and thus functions. The effect of sequence in metal ion induced folding of peptide/protein is important in the design of new functional protein structures, such as biomimetics. In this paper, a set of hairpin peptides with identical composition but different histidine locations have been designed to exploit the metal ion-mediated peptide intramolecular folding transformation through the adjustment of histidine and lysine residue locations. The results demonstrated that the histidine positions in peptide sequence could dramatically affect the coordination modes between peptides and Cu(II) ion. The Cu(II) coordination could affect the secondary structure transformation and self-assembly along with electrostatic interaction and hydrogen bonding synergistically. Three molecules with VHVH sequence at each side of the turn segment (V D PPT) were apt to coordinate with Cu(II) ion with three or four histidines. The closer the VHVH motifs were to the turn segment, the more easier the molecules were to form β sheet structure with the promotion of Cu(II) ions. These results demonstrated that the purposeful location of key amino acids in peptides could achieve the controllable conformation transformation of hairpin peptides, which provides useful strategies for biomimetic design, such as metalloenzymes. Graphical
Phototriggers are useful molecular tools to initiate reactions in enzymes by light for the purpose of photoenzymatic design and mechanistic investigations. Here, we incorporated the non-natural amino acid 5-cyanotryptophan (W 5CN ) in a polypeptide scaffold and resolved the photochemical reaction of the W 5CN –W motif using femtosecond transient UV/Vis and mid-IR spectroscopy. We identified a marker band of ∼2037 cm −1 from the CN stretch of the electron transfer intermediate W 5CN ·− in the transient IR measurement and found UV/Vis spectroscopic evidence for the W ·+ radical at 580 nm. Through kinetic analysis, we characterized that the charge separation between the excited W 5CN and W occurs in 253 ps, with a charge-recombination lifetime of 862 ps. Our study highlights the potential use of the W 5CN –W pair as an ultrafast phototrigger to initiate reactions in enzymes that are not light-sensitive, making downstream reactions accessible to femtosecond spectroscopic detection.
Given the distinct pathological features of neoplasm tissues, multifunctional responsive nanocarriers have been recently considered as promising candidates to optimize the chemotherapy regime. As a result, we propose a graphene oxide-based pH-responsive drug delivery system via covalent assembly of “hairpin-like” cell penetrating peptides with acid sensitive and charge reversal properties to realize superior tumor specificity and lower toxicity. Graphene oxide here can serve as high doxorubicin-loading nanosheets and facilitate swift drug release in response to laser irradiation, which provides an efficient platform for the synergy of photo-chemotherapy. Structurally, polyglycol conjugation on the graphene oxide surface fulfils the function of nanocomposite stabilization. After administration, the elaborately acid sensitive cell penetrating peptides maintain the hairpin structure under physiological conditions, while after entering the tumor acidic microenvironment, they undergo charge reversal and structural conversion to promote the cellular uptake of nanoparticles. The evaluation of nanocomposites in vitro revealed their negligible systematic toxicity and remarkable antitumor effects. In vivo experiments also confirmed the impressive stability and tumor-specific targeting for alleviating breast cancer. In conclusion, hairpin peptide modified graphene oxide nanoparticles show multiple merits including high drug carrying capacity, selective tumor penetration, responsive drug release and effective combination oncotherapy.
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