Biophysics is an interdisciplinary science that applies the theories and methods of physics to understand biological systems. It encompasses a wide range of topics, from the molecular mechanisms within cells to the physical properties of organisms and ecosystems. The goal of biophysics is to uncover the physical principles underlying the structure and function of biological molecules, cells, and cellular systems, providing a deeper understanding of life itself. The Institute of Biophysics, Czech Academy of Sciences (IBP) stands as a beacon of excellence in the field of biophysical research in the Czech Republic. This article delves into its history, structure, research areas, and major scientific achievements, highlighting the role of IBP in the global scientific community.

• Klíčová slova
• Biophysical methods, Biophysics, DNA damage repair, Ionizing radiation, Radiotherapy,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Sparsely tested group of platinum nanoparticles (PtNPs) may have a comparable effect as complex platinum compounds. The aim of this study was to observe the effect of PtNPs in in vitro amplification of DNA fragment of phage λ, on the bacterial cultures (Staphylococcus aureus), human foreskin fibroblasts and erythrocytes. In vitro synthesized PtNPs were characterized by dynamic light scattering (PtNPs size range 4.8-11.7 nm), zeta potential measurements (-15 mV at pH 7.4), X-ray fluorescence, UV/vis spectrophotometry and atomic absorption spectrometry. The PtNPs inhibited the DNA replication and affected the secondary structure of DNA at higher concentrations, which was confirmed by polymerase chain reaction, DNA sequencing and DNA denaturation experiments. Further, cisplatin (CisPt), as traditional chemotherapy agent, was used in all parallel experiments. Moreover, the encapsulation of PtNPs in liposomes (LipoPtNPs) caused an approximately 2.4x higher of DNA damage in comparison with CisPt, LipoCisPt and PtNPs. The encapsulation of PtNPs in liposomes also increased their antibacterial, cytostatic and cytotoxic effect, which was determined by the method of growth curves on S. aureus and HFF cells. In addition, both the bare and encapsulated PtNPs caused lower oxidative stress (determined by GSH/GSSG ratio) in the human erythrocytes compared to the bare and encapsulated CisPt. CisPt was used in all parallel experiments as traditional chemotherapy agent.

• MeSH
• buněčné linie MeSH
• erytrocyty účinky léků   MeSH
• fibroblasty účinky léků   MeSH
• kovové nanočástice škodlivé účinky   chemie   MeSH
• kultivované buňky MeSH
• lidé MeSH
• oxidační stres MeSH
• platina škodlivé účinky   chemie   MeSH
• poškození DNA * MeSH
• replikace DNA * MeSH
• Staphylococcus aureus účinky léků   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• platina MeSH

The cisplatin analogues cis-[PtCl2(3ClHaza)2] (1) and cis-[PtCl2(3IHaza)2] (2) (3ClHaza and 3IHaza are 3-chloro-7-azaindole and 3-iodo-7-azaindole, respectively) are quite toxic to ovarian tumor cells, with moderately better IC50 values than for cisplatin in the cisplatin-sensitive cell line A2780. We investigated potential factors which might be involved in the mechanism underlying the cytotoxic effects of 1 and 2 and compared these factors with those involved in the mechanism underlying the effects of conventional cisplatin. Our data indicate that the higher cytotoxicity of 1 and 2 originates mainly from their efficient cellular accumulation, different effects at the level of cell cycle regulation, and reduced propensity for DNA adduct repair. Studies of their reactivity toward cellular components reveal efficient binding to DNA, which is typically required for an active platinum drug. Further results suggest that 1 and 2 are capable of circumventing resistance to cisplatin induced by alterations in cellular accumulation and DNA repair. Hence, the latter two factors appear to be responsible for differences in the toxicity of 1 or 2, and cisplatin in tumor cells. The results of this work reinforce the idea that direct analogues of conventional cisplatin-containing halogeno-substituted 7-azaindoles offer much promise for the design of novel therapeutic agents.

• MeSH
• apoptóza účinky léků   MeSH
• buněčný cyklus účinky léků   MeSH
• glutathion chemie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• oprava DNA MeSH
• organoplatinové sloučeniny chemie   toxicita   MeSH
• poškození DNA účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• glutathion MeSH
• organoplatinové sloučeniny MeSH

Reported herein is a detailed biochemical and molecular biophysics study of the molecular mechanism of action of antitumor dinuclear Pt(II) complex [{PtCl(DACH)}(2)-mu-Y](4+) [DACH=1,2-diaminocyclohexane, Y=H(2)N(CH(2))(6)NH(2)(CH(2))(2)NH(2)(CH(2))(6)NH(2)] (complex 1). This new, long-chain bifunctional dinuclear Pt(II) complex is resistant to metabolic decomposition by sulfur-containing nucleophiles. The results show that DNA adducts of 1 can largely escape repair and yet inhibit very effectively transcription so that they should persist longer than those of conventional cisplatin. Hence, they could trigger a number of downstream cellular effects different from those triggered in cancer cells by DNA adducts of cisplatin. This might lead to the therapeutic effects that could radically improve chemotherapy by platinum complexes. In addition, the findings of the present work make new insights into mechanisms associated with antitumor effects of dinuclear/trinuclear Pt(II) complexes possible.

• MeSH
• bezbuněčný systém MeSH
• DNA chemie   MeSH
• fluorescence MeSH
• glutathion chemie   MeSH
• konformace nukleové kyseliny * MeSH
• molekulární sekvence - údaje MeSH
• oprava DNA MeSH
• organoplatinové sloučeniny chemie   farmakologie   MeSH
• protinádorové látky chemie   farmakologie   MeSH
• sekvence nukleotidů MeSH
• síra chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA MeSH
• glutathion MeSH
• organoplatinové sloučeniny MeSH
• protinádorové látky MeSH
• síra MeSH

We studied the effect of antitumor cisplatin and inefficient transplatin on the structure and stability of G quadruplexes formed by the model human telomere sequence 5'-GGG(TTAGGG)(3)-3' using circular dichroism, UV-monitored thermal denaturation, and gel electrophoresis. In addition, to investigate whether there is a connection between the ability of cisplatin or transplatin to affect telomerase activity and stability of G quadruplexes, we also used a modified telomere repeat amplification protocol assay that uses an oligonucleotide substrate for telomerase elongation susceptible to forming a G quadruplex. The results indicate that cisplatin is more efficient than transplatin in disturbing the quadruplex structure, thereby precluding telomeric sequences from forming quadruplexes. On the other hand, the results of this work also demonstrate that in absence of free platinum complex, DNA adducts of antitumor cisplatin inhibit telomerase catalysis, so the mechanism underlying this inhibition does not involve formation of the G quadruplexes which are not elongated by telomerase.

• MeSH
• adukty DNA účinky léků   genetika   metabolismus   MeSH
• biokatalýza MeSH
• cirkulární dichroismus MeSH
• cisplatina chemie   farmakologie   MeSH
• denaturace nukleových kyselin MeSH
• elektroforéza v polyakrylamidovém gelu MeSH
• G-kvadruplexy účinky léků   MeSH
• lidé MeSH
• protinádorové látky chemie   farmakologie   MeSH
• sekvence nukleotidů MeSH
• spektrofotometrie ultrafialová MeSH
• techniky amplifikace nukleových kyselin MeSH
• telomerasa antagonisté a inhibitory   metabolismus   MeSH
• telomery chemie   genetika   MeSH
• tranzitní teplota MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adukty DNA MeSH
• cisplatina MeSH
• protinádorové látky MeSH
• telomerasa MeSH
• transplatin MeSH Prohlížeč

The global modification of mammalian and plasmid DNAs by the novel platinum compounds cis-[PtCl(2)(isopropylamine)(1-methylimidazole)] and trans-[PtCl(2)(isopropylamine)(1-methylimidazole)] and the reactivity of these compounds with reduced glutathione (GSH) were investigated in cell-free media using various biochemical and biophysical methods. Earlier cytotoxicity studies had revealed that the replacement of the NH(3) groups in cisplatin by the azole and isopropylamine ligands lowers the activity of cisplatin in both sensitive and resistant cell lines. The results of the present work show that this replacement does not considerably affect the DNA modifications by this drug, recognition of these modifications by HMGB1 protein, their repair, and reactivity of the platinum complex with GSH. These results were interpreted to mean that the reduced activity of this analog of cisplatin in tumor cell lines is due to factors that do not operate at the level of the target DNA. In contrast, earlier studies had shown that the replacement of the NH(3) groups in the clinically ineffective trans isomer (transplatin) by the azole and isopropylamine ligands results in a radical enhancement of its activity in tumor cell lines. Importantly, this replacement also markedly alters the DNA binding mode of transplatin, which is distinctly different from that of cisplatin, but does not affect reactivity with GSH. Hence, the results of the present work are consistent with the view and support the hypothesis systematically tested by us and others that platinum drugs that bind to DNA in a fundamentally different manner from that of conventional cisplatin may have altered pharmacological properties.

• MeSH
• bezbuněčný systém MeSH
• cirkulární dichroismus MeSH
• DNA chemie   účinky léků   MeSH
• glutathion chemie   účinky léků   MeSH
• kultivační média chemie   MeSH
• lidé MeSH
• organoplatinové sloučeniny chemie   farmakologie   MeSH
• protinádorové látky chemie   farmakologie   MeSH
• spektrofotometrie ultrafialová MeSH
• stereoizomerie MeSH
• vazebná místa MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• dichloro(isopropylamine)(1-methylimidazole)diplatinum(II) MeSH Prohlížeč
• DNA MeSH
• glutathion MeSH
• kultivační média MeSH
• organoplatinové sloučeniny MeSH
• protinádorové látky MeSH

Clinically ineffective transplatin [trans-diamminedichloridoplatinum(II)] is used in the studies of the structure-pharmacological activity relationship of platinum compounds. In addition, a number of transplatin analogs exhibit promising toxic effects in several tumor cell lines including those resistant to conventional antitumor cisplatin. Moreover, transplatin-modified oligonucleotides have been shown to be effective modulators of gene expression. Owing to these facts and because DNA is also considered the major pharmacological target of platinum complexes, interactions between transplatin and DNA are of great interest. We examined, using biophysical and biochemical methods, the stability of 1,3-GNG intrastrand cross-links (CLs) formed by transplatin in short synthetic oligodeoxyribonucleotide duplexes and natural double-helical DNA. We have found that transplatin forms in double-helical DNA 1,3-GNG intrastrand CLs, but their stability depends on the sequence context. In some sequences the 1,3-GNG intrastrand CLs formed by transplatin in double-helical DNA readily rearrange into interstrand CLs. On the other hand, in a number of other sequences these intrastrand CLs are relatively stable. We show that the stability of 1,3-GNG intrastrand CLs of transplatin correlates with the extent of conformational distortion and thermodynamic destabilization induced in double-helical DNA by this adduct.

• MeSH
• biofyzikální jevy * MeSH
• cisplatina metabolismus   MeSH
• DNA chemie   genetika   metabolismus   MeSH
• kalorimetrie MeSH
• konformace nukleové kyseliny MeSH
• oligodeoxyribonukleotidy chemie   genetika   metabolismus   MeSH
• reagencia zkříženě vázaná metabolismus   MeSH
• sekvence nukleotidů MeSH
• termodynamika MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cisplatina MeSH
• DNA MeSH
• oligodeoxyribonukleotidy MeSH
• reagencia zkříženě vázaná MeSH
• transplatin MeSH Prohlížeč

Three potential anticancer agents {trans-[PtCl(2)(NH(3))(thiazole)], cis-[PtCl(2)(NH(3))(piperidine)], and PtCl(2)(NH(3))(cyclohexylamine) (JM118)} were explored and compared with cisplatin and the inactive [PtCl(dien)](+) complex. Basic electronic properties, bonding and stabilization energies were determined, and thermodynamic and kinetic parameters for the aquation reaction were estimated at the B3LYP/6-311++G(2df,2pd) level of theory. Since the aquation process represents activation of these agents, the obtained rate constants were compared with the experimental IC(50) values for several tumor cells. Despite the fact that the processes in which these drugs are involved and the way in which they affect cells are very complex, some correlations can be deduced.

• MeSH
• chemické modely * MeSH
• cisplatina chemie   farmakologie   MeSH
• elektrony MeSH
• inhibiční koncentrace 50 MeSH
• kinetika MeSH
• lidé MeSH
• ligandy MeSH
• nádorové buněčné linie MeSH
• organoplatinové sloučeniny chemie   farmakologie   MeSH
• počítačová simulace * MeSH
• protinádorové látky chemie   farmakologie   MeSH
• sloučeniny platiny chemie   MeSH
• termodynamika MeSH
• thiazoly chemie   farmakologie   MeSH
• voda chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• amminedichloro(cyclohexylamine)platinum(II) MeSH Prohlížeč
• cisplatina MeSH
• ligandy MeSH
• organoplatinové sloučeniny MeSH
• platinum chloride MeSH Prohlížeč
• protinádorové látky MeSH
• sloučeniny platiny MeSH
• thiazoly MeSH
• trans-(PtCl2(NH3)(thiazole)) MeSH Prohlížeč
• voda MeSH

[Fe(2)L(3)](4+) (L = C(25)H(20)N(4)) is a synthetic tetracationic supramolecular cylinder (with a triple helical architecture) that targets the major groove of DNA and can bind to DNA Y-shaped junctions. To explore the DNA-binding mode of [Fe(2)L(3)](4+), we examine herein the interactions of pure enantiomers of this cylinder with DNA by biochemical and molecular biology methods. The results have revealed that, in addition to the previously reported bending of DNA, the enantiomers extensively unwind DNA, with the M enantiomer being the more efficient at unwinding, and exhibit preferential binding to regular alternating purine-pyrimidine sequences, with the M enantiomer showing a greater preference. Also, interestingly, the DNA binding of bulky cylinders [Fe(2)(L-CF(3))(3)](4+) and [Fe(2)(L-Ph)(3)](4+) results in no DNA unwinding and also no sequence preference of their DNA binding was observed. The observation of sequence-preference in the binding of these supramolecular cylinders suggests that a concept based on the use of metallosupramolecular cylinders might result in molecular designs that recognize the genetic code in a sequence-dependent manner with a potential ability to affect the processing of the genetic code.

• MeSH
• deoxyribonukleasa I MeSH
• DNA footprinting MeSH
• DNA chemie   metabolismus   MeSH
• ethidium chemie   MeSH
• kompetitivní vazba MeSH
• konformace nukleové kyseliny MeSH
• pyridiny chemie   MeSH
• restrikční enzymy metabolismus   MeSH
• sekvence nukleotidů MeSH
• stereoizomerie MeSH
• superhelikální DNA chemie   MeSH
• železnaté sloučeniny chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• deoxyribonukleasa I MeSH
• DNA MeSH
• ethidium MeSH
• pyridiny MeSH
• restrikční enzymy MeSH
• superhelikální DNA MeSH
• železnaté sloučeniny MeSH

The impressive impact of cisplatin on cancer on one side and severe side effects, as well as the development of drug resistance during treatment on the other side, were the factors motivating scientists to design and synthesize new more potent analogues lacking disadvantages of cisplatin. Platinum(IV) complexes represent one of the perspective groups of platinum-based drugs. In this review, we summarize recent findings on both in vitro and in vivo effects of platinum(IV) complexes with adamantylamine. Based on a literary overview of the mechanisms of activity of platinum-based cytostatics, we discuss opportunities for modulating the effects of novel platinum complexes through interactions with apoptotic signaling pathways and with cellular lipids, including modulations of the mitochondrial cell death pathway, oxidative stress, signaling of death ligands, lipid metabolism/signaling, or intercellular communication. These approaches might significantly enhance the efficacy of both novel and established platinum-based cytostatics.

• Publikační typ
• časopisecké články MeSH