Poly-histidine grafting leading to fishbone-like architectures

Abstract

A small series of Morita-Baylis-Hillman adduct (MBHA) derivatives was synthesized and made to react with imidazole, N-acetylhistidine, and N-acetylhexahistidine as models of poly-histidine derivatives. Intriguingly, the reaction of MBHA derivatives 1a and b with imidazole in acetonitrile-phosphate buffered saline (PBS) gave the imidazolium salt biadducts 3a and b as the main reaction products. These results were confirmed by experiments performed with N-acetylhistidine and 1b and suggested the possible occurrence of these structures in the products of poly-histidine labeling with MBHA derivatives 1a and b.These compounds were then transformed into the corresponding water-soluble derivatives 1c-e by introducing oligo(ethylene glycol) chains and their reactivity was evaluated in preliminary experiments with imidazole and then with N-acetylhexahistidine in PBS. The structure of polymeric materials Ac-His-6-MBHA-1d and Ac-His-6-MBHA-1e obtained using ten-fold excesses of compounds 1d and e was investigated using mass spectrometry, NMR spectroscopy, and photophysical studies, which suggested the presence of biadduct residues in both polymeric materials. These results provide the basis for the preparation of fishbone-like polymer brushes, the characterization of their properties, and the exploration of their potential applications in different fields of science such as in vivo fluorogenic labeling, fluorescence microscopy, protein PEGylation, up to the production of smart materials and biosensors.

Gene delivery by peptide-assisted transport

“…, listeriolysin O, pneumococcal pneumolysin, virus inspired polymer for endosomal release (VIPER)] [38,39]; the proton sponge effect ( e.g. , histidine-rich peptides) [40]; or conformational changes in peptide secondary structure that assist membrane insertion and endosomal escape ( e.g. , hemagglutin derived peptide HA2, INF7, GALA) [41].…”

Xanthopsin‐Like Systems via Site‐Specific Click‐Functionalization of a Retinoic Acid Binding Protein

“…MBHA derivatives 2 a and 4 were synthesized as reported in the literature, (Refs. [35] and [31]). MBHA derivative 8 was prepared by modifying a previously published procedure (Scheme 1).…”

“…A mixture of MBHA acetate 2 a [35] (53 mg, 0.172 mmol) in chloroform (5.0 mL) containing n-butylamine (0.080 mL, 0.859 mmol) was stirred at room temperature for 2 h. The reaction mixture was concentrated under reduced pressure and the resulting residue was purified by flash chromatography with petroleum ether-ethyl acetate (8 : 2) as the eluent to obtain pure amine derivative 3 as a pale-yellow oil (38 mg, yield 69 %). 1…”

“…In the past MBHAs have been employed as reagents in imidazole modification. [31][32][33] Some of these reagents were prepared [34,35] and characterized [36,37] in our laboratory (i. e. 1 a-c and 2 a-e, Figure 1A). However, only functionalization of nucleophilic residues (i. e. histidine) belonging to a peptide chain and/or residing on protein tails were targeted.…”

“…As shown in bold in Figure 1A and 1B, the achieved functionalization would generate unnatural prosthetic groups incorporating the framework of natural chromophores such as that of the photoactive yellow protein (PYP), [35] the most thoroughly characterized blue-light eubacterial photoreceptor belonging to the xanthopsin family. This observation together with the fact that certain PYP constructs have, for instance, been employed to modulate the genetic expression via light irradiation, [38] provides a realistic route to flexible syntheses of novel optogenetic tools as well as to the development of a "lab-on-a-molecule" concept: a prospective tool for the systematic study of the effects of the position and orientation of amino acid residues on synthetic chromophores.…”