Conformational Transition-Triggered Disassembly of Therapeutic Peptide Nanomedicine for Tumor Therapy.

Cationic therapeutic peptides have received widespread attention due to their excellent antibacterial and antitumor properties. However, most of these peptides have undesirable delivery efficiency and high hemolytic toxicity due to the positively charged α-helix structure containing many lysine and arginine, which may restrict its in vivo applications. Herein, a conformationally transformed therapeutic peptide Pep-HCO3 modified with bicarbonates on guanidine groups is designed. Such a design allows Pep-HCO3 ((nap-RAGLQFPVGRLLRRLLRRLLR) nHCO3 ) to self-assemble into nanoparticles (NP-Pep) due to disrupting helix folding and the formation of intermolecular hydrogen bonding between bicarbonates and guanidine groups. When pH is from 7.4 to 6.5 at the tumor sites, guanidine bicarbonate can be hydrolyzed to form CO2 and guanidine groups, resulting in the disassembling of the NP-Pep into monomers α-Pep with a positively charged α-helix structure. In vivo, NP-Pep not only inhibits the tumor growth of xenografted mice with a twofold enhanced inhibition rate compared with α-Pep treatment group, but also significantly reduces the hemolytic toxicity by responding to the pH of tumor microenvironment. Therefore, the strategy of conformational transition-triggered disassembly of nanoparticles allows efficient delivery of cationic therapeutic peptides and lowering the hemolytic toxicity, which may provide an avenue for developing high-performance cationic peptide in vivo applications.

Self-assembly behavior of tail-to-tail superstructure formed by mono-6-O-(4-carbamoylmethoxy-benzoyl)-ß-cyclodextrin in solution and the solid state.

A novel mono-modified ß-cyclodextrin (ß-CD) consisting of 4-carbamoylmethoxy-benzoyl unit at the primary side was synthesized and its self-assembly behavior was determined by X-ray crystallography and NMR spectroscopy. The crystal structure shows a 'Yin-Yang'-like packing mode, in which the modified ß-CD exhibits a channel superstructure formed by a tail-to-tail dimer as the repeating motif with the substituted group embedded within the hydrophobic cavity of the facing ß-CD. The geometry of the substituted group is determined by the inclusion of the cavity and is further stabilized by two intermolecular hydrogen bonds between the carbonyl O atom and phenyl group. Furthermore, NMR ROESY investigation indicates that the self-assembly behavior of the substituted group within the ß-CD cavity is retained in aqueous solution, and the effective binding constant Ka was calculated to be 1330 M(-1) by means of (1)H NMR titration according to iterative determination.

(E)-5-[(1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)imino-meth-yl]-2-methoxy-phenyl 4-bromo-benzene-sulfonate.

In the title compound, C(25)H(22)BrN(3)O(5)S, the central benzene ring makes dihedral angles of 32.02 (14), 37.49 (18) and 80.52 (13)°, respectively, with the pyrazolone ring, the bromo-benzene ring and the terminal phenyl ring. This conformation features a short intramolecular C-H⋯O contact that generates an S(6) ring. In the crystal, inversion dimers linked by pairs of C-H⋯O=C hydrogen bonds occur.

An investigation of the inclusion complex of beta-cyclodextrin with p-nitrobenzoic acid in the solid state.

The weak inclusion complex of cyclomaltoheptaose (beta-cyclodextrin, betaCD) with p-nitrobenzoic acid was investigated in the solid state. Crystallography shows that two betaCD molecules co-crystallize with two p-nitrobenzoic acids and 28.5 water molecules [2(C(42)H(70)O(35))x2(C(7)H(5)NO(4))x28.5H(2)O] in the triclinic system.

Protein-imprinted polymer with immobilized assistant recognition polymer chains.

Here we introduce a new method for preparing a protein-imprinted polymer with immobilized assistant recognition polymer chains as an additional element of monomer to create effective recognition sites. In this work the bovine serum albumin was used as template and the template protein was selectively assembled with immobilized assistant recognition polymer chains from their library, numerous limited length polymer chains with randomly distributed recognition sites and immobilizing sites. These assemblies of protein and immobilized assistant recognition polymer chains would be adsorbed by the macro porous adsorbent spheres and immobilized by cross-linking polymerization. After removing the template, binding sites that were complementary to the target protein in size, shape and position of recognition groups were exposed, and their confirmation was preserved by the cross-linked structure. The synthesized imprinted polymer was used to adsorb BSA from protein mixtures, and showed a high selectivity.

Encapsulation of quinine by beta-cyclodextrin: excellent model for mimicking enzyme-substrate interactions.

An inclusion complex formed by beta-cyclodextrin and quinine has been investigated in solution and in the solid state, in which the quinoline ring and the aliphatic ring locate in different hydrophobic cavities, respectively. The study on the inclusion geometry and weak interactions shows that the difference in conformation for this complex is a result of three main packing arrangement considerations, which can provide an ideal model mimicking enzyme-substrate interactions.