Distinctive Nucleic Acid Recognition by Lysine-Embedded Phenanthridine Peptides.

Three new phenanthridine peptide derivatives (, , and ) were synthesized to explore their potential as spectrophotometric probes for DNA and RNA. UV/Vis and circular dichroism (CD) spectra, mass spectroscopy, and computational analysis confirmed the presence of intramolecular interactions in all three compounds. Computational analysis revealed that compounds alternate between bent and open conformations, highlighting the latter's crucial influence on successful polynucleotide recognition.

Sulfone-based human liver pyruvate kinase inhibitors - Design, synthesis and in vitro bioactivity.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent pathological condition characterised by the accumulation of fat in the liver. Almost one-third of the global population is affected by NAFLD, making it a significant health concern. However, despite its prevalence, there is currently no approved drug specifically designed for the treatment of NAFLD.

Membrane Separation of Chicken Byproduct Hydrolysate for Up-Concentration of Bioactive Peptides.

Membrane processes, such as microfiltration, ultrafiltration, and nanofiltration, are increasingly used for various applications in both upstream and downstream processing. Membrane-based processes play a critical role in the field of separation/purification of biotechnological products, including protein production/purification. The possibility of using membranes to separate peptides from a chicken byproduct hydrolysate and the effect of the performed downstream processing on the DPP-IV dipeptidyl peptidase IV (DPP-IV) inhibitory activity of mechanical deboning chicken residue (MDCR) has been investigated.

The role of biospectroscopy and chemometrics as enabling technologies for upcycling of raw materials from the food industry.

It is important to utilize the entire animal in meat and fish production to ensure sustainability. Rest raw materials, such as bones, heads, trimmings, and skin, contain essential nutrients that can be transformed into high-value products. Enzymatic protein hydrolysis (EPH) is a bioprocess that can upcycle these materials to create valuable proteins and fats.

The Mechanism of Anti-Tumor Activity of 6-Morpholino- and 6-Amino-9-Sulfonylpurine Derivatives on Human Leukemia Cells.

The aim of this study was to explore the mechanism of antitumor effect of ()-6-morpholino-9-(styrylsulfonyl)-9-purine (6-Morpholino-SPD) and ()-6-amino-9-(styrylsulfonyl)-9-purine (6-Amino-SPD). The effects on apoptosis induction, mitochondrial potential, and accumulation of ROS in treated K562 cells were determined by flow cytometry. The RT-PCR method was used to measure the expression of , , , and genes, as well as selected miRNAs.

Exploration of Novel Urolithin C Derivatives as Non-Competitive Inhibitors of Liver Pyruvate Kinase.

The inhibition of liver pyruvate kinase could be beneficial to halt or reverse non-alcoholic fatty liver disease (NAFLD), a progressive accumulation of fat in the liver that can lead eventually to cirrhosis. Recently, urolithin C has been reported as a new scaffold for the development of allosteric inhibitors of liver pyruvate kinase (PKL). In this work, a comprehensive structure-activity analysis of urolithin C was carried out.

Phenanthridine-pyrene conjugates as fluorescent probes for DNA/RNA and an inactive mutant of dipeptidyl peptidase enzyme.

Two novel conjugate molecules were designed: pyrene and phenanthridine-amino acid units with a different linker length between the aromatic fragments. Molecular modelling combined with spectrophotometric experiments revealed that in neutral and acidic buffered water solutions conjugates predominantly exist in intramolecularly stacked conformations because of the π-π stacking interaction between pyrene and phenanthridine moieties. The investigated systems exhibited a pH-dependent excimer formation that is significantly red-shifted relative to the pyrene and phenanthridine fluorescence.

Anthraquinone derivatives as ADP-competitive inhibitors of liver pyruvate kinase.

Liver pyruvate kinase (PKL) is a major regulator of metabolic flux and ATP production during liver cell glycolysis and is considered a potential drug target for the treatment of non-alcoholic fatty liver disease (NAFLD). In this study, we report the first ADP-competitive PKL inhibitors and identify several starting points for the further optimization of these inhibitors. Modeling and structural biology guided the optimization of a PKL-specific anthraquinone-based compound.

6-Morpholino- and 6-amino-9-sulfonylpurine derivatives. Synthesis, computational analysis, and biological activity.

The synthesis of novel 6-chloro/morpholino/amino/-9-sulfonylpurine derivatives was accomplished in two ways, either (i) involving the condensation reaction of 6-chloropurine with commercially available arylsulfonyl chlorides in acetone and the presence of aqueous KOH at 0 °C, followed by the substitution of C6-chlorine with morpholine, or (ii) employing a reversed synthetic approach where 6-morpholinopurine and commercially available adenine bases were reacted with the corresponding alkyl, 2-arylethene and arylsulfonyl chlorides giving the N9 sulfonylated products, the latter particularly used where prior nonselective sulfonylation was observed. In both approaches, the sulfonylation reaction occurred regioselectively at the purine N9 position lacking any concurrent N7 derivatives, except in the case of a smaller methyl substituent on SO and the free amino group at C6 of the purine ring. The tautomeric features of initial N9 unsubstituted purines, as well as stability trends among the prepared -9-sulfonylpurine derivates, were investigated using DFT calculations with an important conclusion that electron-donating C6 substituents are beneficial for the synthesis as they both promote the predominance of the desired N9 tautomers and help to assure the stability of the final products.

Flexibility and Preorganization of Fluorescent Nucleobase-Pyrene Conjugates Control DNA and RNA Recognition.

We synthesized a new amino acid-fluorescent nucleobase derivative (qAN1-AA) and from it two new fluorescent nucleobase-fluorophore (pyrene) conjugates, whereby only the analogue with the longer and more flexible linker (qAN1-pyr2) self-folded into intramolecularly stacked qAN1/pyrene conformation, yielding characteristic, 100 nm-red-shifted emission (λ = 500 nm). On the contrary, the shorter and more rigid linker resulted in non-stacked conformation (qAN1-pyr1), characterized by the emission of free pyrene at λ = 400 nm. Both fluorescent nucleobase-fluorophore (pyrene) conjugates strongly interacted with ds-DNA/RNA grooves with similar affinity but opposite fluorescence response (due to pre-organization), whereas the amino acid-fluorescent base derivative (qAN1-AA) was inactive.

DNA/RNA recognition controlled by the glycine linker and the guanidine moiety of phenanthridine peptides.

The binding of four phenanthridine-guanidine peptides to DNA/RNA was evaluated via spectrophotometric/microcalorimetric methods and computations. The minor structural modifications-the type of the guanidine group (pyrrole guanidine (GCP) and arginine) and the linker length (presence or absence of glycine)-greatly affected the conformation of compounds and consequently the binding to double- (ds-) and single-stranded (ss-) polynucleotides. GCP peptide with shorter linker was able to distinguish between RNA (A-helix) and DNA (B-helix) by different circular dichroism response at 295 nm and thus can be used as a chiral probe.

The transformation from 2°-amine to 3°-amine of cyclam ring alters the fragmentation patterns of 1-tosylcytosine-cyclam conjugates.

The novel N-1-sulfonylcytosine-cyclam conjugates 1 and 2 conjugates are ionized by electrospray ionization mass spectrometry (ESI MS) in positive and negative modes (ES and ES ) as singly protonated/deprotonated species or as singly or doubly charged metal complexes. Their structure and fragmentation behavior is examined by collision induced experiments. It was observed that the structure of the conjugate dictated the mode of the ionization: 1 was analyzed in ES mode while 2 in positive mode.

Conjugates of Classical DNA/RNA Binder with Nucleobase: Chemical, Biochemical and Biomedical Applications.

Among the most intensively studied classes of small molecules (molecular weight < 650) in biomedical research are small molecules that non-covalently bind to DNA/RNA, and another intensively studied class is nucleobase derivatives. Both classes have been intensively elaborated in many books and reviews. However, conjugates consisting of DNA/RNA binder covalently linked to nucleobase are much less studied and have not been reviewed in the last two decades.

C5-Morpholinomethylation of N1-sulfonylcytosines by a one-pot microwave assisted Mannich reaction.

A fast and efficient route for the introduction of a methylene bridged-amine (morpholinomethyl) functionality in the C5 position of the sulfonylated cytosine nucleobase has been developed. First, novel N1-sulfonylcytosine derivatives 3-6 were prepared by the condensation of silylated cytosine with selected sulfonyl chlorides. They were subsequently transformed to 5-morpholinomethyl-N1-sulfonylcytosine derivatives (8, 12-15) using microwave irradiation.

Antiproliferative and proapoptotic activity of molecular copper(II) complex of N-1-tosylcytosine.

In an attempt to enhance the previously observed antiproliferative capacity of 1-(p-toluenesulfonyl)cytosine (N-1-tosylcytosine, ligand 1), its copper(II) complex (Cu(1-TsC-N3)Cl, complex 2) was prepared and tested in vitro on various carcinoma and leukemia cells. The comparative in vitro studies using the ligand 1, the complex 2, CuClx2HO salt (salt 3) and the 1:2 mixture of the salt 3 and ligand 1 (mixture 4) were performed on normal (WI38), human carcinoma (HeLa, CaCo2, MiaPaCa2, SW620), lymphoma (Raji) and leukemia (K562) cell lines. Significantly elevated concentration of the intracellular copper after treatment of K562 cells and HeLa cells during 2h with complex 2 (7.

ESI-MS studies of the non-covalent interactions between biologically important metal ions and N-sulfonylcytosine derivatives.

The aim of this report is to present the electrospray ionization mass spectrometry results of the non-covalent interaction of two biologically active ligands, N-1-(p-toluenesulfonyl)cytosine, 1-TsC, 1 and N-1-methanesulfonylcytosine, 1-MsC, 2 and their Cu(II) complexes Cu(1-TsC-N3) Cl , 3 and Cu(1-MsC-N3) Cl and 4 with biologically important cations: Na , K , Ca , Mg and Zn . The formation of various complex metal ions was observed. The alkali metals Na and K formed clusters because of electrostatic interactions.

Advances in Peptide-based DNA/RNA-Intercalators.

Interactions between DNA/RNA and huge variety of peptides are quite common in nature, controlling vast number of processes. Also, there are several naturally occurring small molecules which contain peptide and DNA intercalator in structure, whereby their biological activity is based on synergistic interactions of both components; for instance bis-intercalator echinomycin. Versatility of synthetic approaches to short peptides allowed their usage as simple recognition units within the DNA or RNA grooves or as backbone carriers for variety of bioactive substituents attached to amino acid side chains, one of very popular examples being PNAs.