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Journal Article 2013; 34(6): 573-578 PubMed PMID: 24378453 Citation  Keywords:  Animals, Biocompatible Materials:chemistry, Cattle, Dendrimers:chemistry, Drug Interactions, Hypoglycemic Agents:chemistry, Insulin:chemistry, Protein Binding, Protein Conformation, Spectrometry, Fluorescence, Tyrosine:chemistry,.   

OBJECTIVE: In this study the mechanism of interactions between polyamidoamine (PAMAM) dendrimers and bovine insulin was examined. The insulin is a 51 amino acid peptide-hormone involved in the homeostasis of blood glucose levels. This molecule consists of two chains - A and B - linked by two disulphide bridges. As insulin contains four tyrosine residues it was possible to evaluate dendrimers effect on protein conformation by measuring changes in the fluorescence spectra of insulin after addition of dendrimers or classical quenchers.

METHODS: PAMAM dendrimers are based on ethylenediamine core and branched units which are built from methyl acrylate and ethylenediamine. PAMAM dendrimers with different surface groups (-COOH, -NH2, -OH) were used. Their size is comparable to insulin.

RESULTS: The experiments show that interactions exist between PAMAM dendrimers and insulin. It was found that these interactions depend on a kind of dendrimer surface groups.

CONCLUSIONS: It is very likely that interactions are of electrostatic nature and cause insulin conformational changes....

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Journal Article 2013; 34(Suppl 2): 123-129 PubMed PMID: 24362104 Citation  Keywords:  Animals, Cell Proliferation:drug effects, Estradiol:metabolism, Gene Expression Regulation:drug effects, Humans, Male, Protein Binding:drug effects, Receptors, Estrogen:metabolism, Response Elements:drug effects,.   

: Group of estrogen pollutants, where the highest estrogen activity is reported at estradiol, is characterized by the fact that even at very low concentrations have potential to cause xenoestrogenic effects. During exposure of excessive amounts of estradiols may be produced undesirable effects resulting in the feminization of males of water organisms. The presence of estradiols in drinking water implies also a risk for the human population in the form of cancers of endocrine systems, abnormalities in reproduction or dysfunctions of neuronal and immune system. Currently, the research is focused mainly to uncover the relationship between the estrogen receptors binding affinity with an estrogen response element and estradiol. In this review we summarized facts about molecular biological principles of β estradiol-estrogen receptor complex binding with estrogen response element and its successive effect on cancer genes expression....

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Comparative Study 2009; 30(1): 139-143 PubMed PMID: 19300396 Citation  Keywords:  Animals, Binding, Competitive, Carps:metabolism, Female, Gonadotropin-Releasing Hormone:metabolism, Humans, Mammals:metabolism, Pituitary Gland:metabolism, Protein Binding, Radioactive Tracers, Rats, Receptors, LHRH:metabolism, Salmon:metabolism,.   

OBJECTIVES: Receptor binding of GnRH is connected with the stimulation of pituitary gonadotropic cells leading to both the release and biosynthesis of gonadotropins. The binding is connected with the conformational changes in the receptor which induce the specific intracellular signalisation. The study of fish GnRHs and their receptors may give us new knowledge of the complex interplay of different mechanisms involved in neuroendocrine regulation of reproduction.

METHODS: Receptor binding of both mGnRH and sGnRH were compared by the study utilizing the displacement method with mGnRH or sGnRH as radioactive tracers. Incubation was performed at 2 degrees C to avoid ligand degradation.

RESULTS: The comparative binding of mGnRH and sGnRH with GnRH receptors from the female rat pituitary and female carp pituitary was studied. At the 50% of displacement, the binding of sGnRH to the rat pituitary receptor was very small and in comparison to the binding of mGnRH (100%) was in the range 2-15%. However, the binding of mGnRH to carp pituitary receptors is small in comparison with the binding of sGnRH (100%) and was in the range 5-20%.

CONCLUSION: The results demonstrated the differences in binding of different GnRHs to the receptor in rats and carp. This suggests that the structures of GnRH and its receptor undergo co-evolution in different classes of animals....

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Journal Article 2007; 28(4): 401-405 PubMed PMID: 17693965 Citation  Keywords:  Animals, Cattle, Exons, Genotype, Liver:metabolism, Male, Polymorphism, Single Nucleotide:genetics, Protein Binding:genetics, Receptors, Somatotropin:genetics, Signal Transduction,.   

OBJECTIVES: Nucleotide sequence polymorphisms in the coding gene regions may influence the biological properties of proteins encoded by a gene. The A/T substitution in exon 8 of the growth hormone receptor (GHR) gene results in changed amino acid sequence 279 (Phe/Tyr) in the transmembrane domain of the receptor protein and therefore could influence its functional parameters. We searched for the relationship between the A/T nucleotide polymorphism in the GHR gene the receptor binding capacity and dissociation constant.

METHODS: Nucleotide sequence variations in the exon 8 (coding for the transmembrane domain of the receptor) of the bovine GHR gene and in fragments of adjacent introns were analysed using PCR-SSCP and sequencing techniques. GH receptor binding capacity (Bmax) and dissociation constant (Kd) for GHR were determined by the Scatchard analysis in livers of ten bulls carrying the AA or AT GHR genotypes.

RESULTS: Two single nucleotide polymorphisms (SNPs) were identified--the C/T transition in intron 8 at position 863+32 and the A/T transversion in exon 8 at position 836, the latter resulting in Phe/Tyr amino acid substitution in the receptor protein. The results showed significant differences in the GHR binding capacity between these genotypes. Bmax was significantly greater (p< or =0.01) in bulls carrying TT genotype of GHR in comparison to those with the AT genotype. No significant differences in the dissociation constants (Kd) were found.

CONCLUSION: Our results demonstrated that single base substitution in the transmembrane domain encoding region of GH receptor gene may influence the physiological properties of the receptor....

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Journal Article 2005; 26(3): 237-241 PubMed PMID: 15990728 Citation  Keywords:  Animals, DNA:chemistry, Entropy, Evolution, Molecular, Humans, Models, Chemical, Nucleic Acid Conformation, Peptides:chemistry, Promoter Regions, Genetic, Protein Binding, Protein Conformation, Transcription Factors:chemistry,.   

PROBLEM: Gerontology observations show that ageing of organism is accompanied by the decrease of the chromatin activity and slowing down of the protein synthesis. Natural regulatory oligopeptides and their synthetic analogues take part in the activation of chromatin and normalise rate of the protein synthesis in cultured tissues. Regulatory peptides significantly enhance longevity.

OBJECTIVES: The objective of this work is to find a possible molecular mechanism by which the regulatory peptides influence the part of genetic system is responsible for initiation of protein synthesis in higher organisms.

METHODS: An interdisciplinary approach was used to address the problem. The work involved not only medical scientists and biologists, but also specialists in biopolymer chemistry, and mathematicians for statistical analysis of information interaction of amino acid and nucleotide sequences.

CONCLUSIONS: The structures and metrics of peptides and the DNA double-helix cause the recognition and complementary binding of a regulatory peptide with DNA functional groups at the interface of the major groove. We have used complementary binding model to find a possible base pair sequence ATTTTC for specific binding of synthetic tetrapeptide epitalon. This base pair block and its reverse complement were found repeatedly in the promoter region of telomerase. A comparison of statistical information content of peptides and oligonucleotide sequences shows that these two classes of biopolymers are information carriers and. exchange the information to initiate the gene transcription....

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