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Biomedical subjects

A A Khorlin

Publications and source records attributed to A A Khorlin.

At least 19 recordsLinked to original sources
PubMed1999

Bicyclic monoterpene diols induce differentiation of S91 melanoma and PC12 pheochromocytoma cells by a cyclic guanosine-monophosphate-dependent pathway.

Previously, we showed that 5-norbornene-2,2-dimethanol (5-NBene-2,2-DM) is an effective inducer of melanogenesis in cultured cells and guinea-pig skin [Brown et al. (1998) J. Invest. Dermatol., 110:428-437]. This study shows that 2,3-cis/exo-pinanediol (2,3-cs/ex-PinD) is a more effective inducer of melanogenesis than 5-NBene-2,2-DM in S91 mouse melanoma cells. Furthermore, 2,3-cs/ex-PinD appears to penetrate guinea-pig skin better than 5-NBene-2,2-DM and to induce higher levels of pigmentation. Both 5-NBene-2,2-DM and 2,3-cs/ex-PinD induce synthesis of nitric oxide (NO) in S91 cells, and the melanogenic activity of both compounds is reduced by inhibitors of the NO/cyclic guanosine monophosphate (cGMP)/protein kinase(PK) G signaling pathway, but not by inhibitors of the PKC or PKA pathways. Thus, these bicyclic monoterpene diols appear to induce melanogenesis by the same pathway in S91 cells as that shown previously for ultraviolet radiation in melanocytes (Romero-Graillet et al. (1996) J. Biol. Chem., 271:28052-28056). These compounds also induce NO synthesis, neurite outgrowth, and tyrosine hydroxylase activity in PC12 pheochromocytoma cells. Neurite outgrowth in PC12 cells is blocked by the guanylate cyclase inhibitor, LY83583 (6-anilino-2,8-quinolinequinone), indicating that, similar to S91 cells, the induction of morphological differentiation of PC12 cells by bicyclic monoterpene diols is regulated by a cGMP-dependent pathway.

Animals↗
PubMed1994

Trivaline molecular complexes with trinucleotides form in solution the extended, about 1000 A in length structures.

The fluorescence, flow linear dichroism and electron microscopy (EM) have shown the trivaline ability to interact in solution with certain molecules of trinucleotides. This interaction results in formation of extended structures up to several thousand angstroms in length. Such structures were observed for trivaline complexes with homopurine, homopyrimidine or random sequences of deoxyribo- and ribonucleotides, independently of the presence or absence of the terminal 5'-phosphate residue. A model of such a structural organization is proposed. An elementary structural unit consists of a trivaline beta-dimer and adsorbed trinucleotide. So, "dimeric" complex is formed. Two such "dimeric" complexes combine with each other by means of peptide-peptide contacts (as with beta-sandwich). So, "tetrameric" complex is formed. It has a dyad axis. Two such structural units combine with each other by means of Hoogsteen's hydrogen bonds. So, "octameric" complex is formed. It has three mutually perpendicular dyad axes. The "octameric" complexes appear to be able to combine with each other by means of stacking interactions, and to form the regular organized aggregates consisting of many dozens of elementary units. So, "stacking" structure is formed. The "octameric" complex is the symmetry translational unit of such a structure. The spatial position of the bases in all these structures is additionally fixed by the nucleo-peptide interactions. These aggregates have the appearance of extended structures on electron micrographs.

Microscopy, Electron↗
PubMed1992

Trivaline 'catalyzes' 5'-pdGTT oligomerization in solution.

We have found that the 5'-pdGTT molecules at a concentration of 10(-4) M are oligomerized in solution in the presence of 10(-4) M tripeptide-(L-Val)3-NH-NH-DNS.CF3COOH and the condensation reagents (carbodiimide and imidazole). Oligonucleotides not less than 12 bases long were formed in the yield which was over 15%. It is known that in the absence of peptide 10(-2) M mono- or dinucleotides are required. Thus trivaline can be considered as one of the simplest enzymes. This oligomerization seems to be an essential way for the synthesis of long enough oligonucleotides of the random GC-sequence, which could be used at the earliest steps of evolution.

Catalysis↗
PubMed1991

A method for DNA sequencing by hybridization with oligonucleotide matrix.

A new technique of DNA sequencing by hybridization with oligonucleotide matrix (SHOM) which could also be applied for DNA mapping and fingerprinting, mutant diagnostics, etc., has been tested in model experiments. A dot matrix was prepared which contained 9 overlapping octanucleotides (8-mers) complementary to a common 17-mer. Each of the 8-mers was immobilized as individual dot in thin layer of polyacrylamide gel fixed on a glass plate. The matrix was hybridized with the 32P-labeled 17-mer and three other 17-mers differing from the first one by a single base change. The hybridization enabled us to distinguish perfect duplexes from those containing mismatches in 32 out of 35 cases. These results are discussed with respect to the applicability of the approach for sequencing. It was shown that hybridization of DNA with an immobilized 8-mer in the presence of a labeled 5-mer led to the formation of a stable duplex with the 5-mer only if the 5- and the 8-mers were in continuous stacking making a perfect nicked duplex 13 (5+8) base pairs long. These experiments and computer simulations suggest that continuous stacking hybridization may increase the efficiency of sequencing so that random or natural coding DNA fragments about 1000 bases long could be sequenced in more than 97% of cases. Miniaturized matrices or sequencing chips were designed, where oligonucleotides were immobilized within 100 x 100 micron dots disposed at 100 micron intervals. Hybridization of fluorescently labeled DNA fragments with microchips may simplify sequencing and ensure sensitivity of at least 10 attomoles per dot. The perspectives and limitations of SHOM are discussed.

Base Sequence↗
PubMed1990

[Compounds similar to acyclovir. VII. Attempts to construct an anti-herpetic agent (6-hydroxy-2-oxa-4-hexenyl derivatives of nucleic bases].

Based on the available data on the acyclovir's mechanism of action we attempted to predict the antiherpetic activity of 6-hydroxy-2-oxahexen-4-yl derivatives of nucleic bases. In terms of this model 9-(6-hydroxy-2-oxahexen-4-yl) guanine might be active. 6-Hydroxy-2-oxahexen-4-yl derivatives of adenine, guanine, cytosine, thymine, uracil, 1,2,4-triazole-3 and 1,2,4-triazole-5-carboxamide have been synthesized and their activity against herpes virus I investigated. The guanine derivative proved to possess rather high activity (chemotherapeutical index 8).

Acyclovir↗
PubMed1990

[Compounds similar to acyclovir. VI. Synthesis of optically active 1',2'-seconucleosides].

A convenient method is suggested of synthesis of (3R, 4R)-, (3S, 4S)- and (3R/S, 4S/R)-dihydroxy-3-hydroxymethyl-2-oxapentyl derivatives of the, cytosine, uracyl, adenine and guanine ("full" acyclic analogues of nucleosides with C1'-C2' bond cleaved) by condensation of trimethylsilyl derivatives of nucleic bases (sodium salt in case of adenine) with (3$, 4R)-, (3S )-, (3S, 4S)- and (3R/S, 4S/R)-4,5-diacetoxy-3-acetoxymethyl-1-chloro-2-oxapentanes without catalyst followed by deacetylation.

Acyclovir↗
PubMed1989

[A simple, convenient method for the synthesis of acyclic analogs of guanosine].

A simple convenient method for the synthesis of guanosine acyclic analogues with the nucleic base attached to the primary carbon atom is proposed. The method involves treatment of trimethylsilyl derivative of guanine with agents of general formula ROCH2Cl in the absence of Lewis acids. 9-Substituted derivatives of guanine were prepared by this method with 50-65% yields.

Chemical Phenomena↗
PubMed1988

Electron microscopic and physico-chemical studies of DNA complexes with synthetic oligopeptides: binding specificity and DNA compact structures.

Binding to DNA of two synthetic peptides, Val-Thr-Thr-Val-Val-NH-NH-Dns and Thr-Val-Thr-Lys-Val-Gly-Thr-Lsy-Val-Gly-Thr-Val-Val-NH-NH-Dns (where Dns is a residue of 5-dimethylaminonaphthalene-1-sulfonic acid), has been studied by circular dichroism, electron microscopy and fluorescence methods. It has been found that these two peptides can self-associate in aqueous solution as follows from the fact that concentration-dependent changes are observed in the UV absorbance and fluorescence spectra. The two peptides can bind to DNA both in self-associated and monomeric forms. The pentapeptide in the beta-associated form binds more strongly to poly(dG).poly(dC) than to poly[d(A-C)].poly[d(G-T)] and poly(dA).poly(dT) whereas the tridecapeptide exhibits an opposite order of preferences binding more strongly to poly[d(A-C)].poly[d(G-T)] and poly(dA).poly(dT) than to poly(dG).poly(dC). Binding is a cooperative process which is accompanied by the DNA compaction at peptide/DNA base pair ratios greater than 1. At the initial stage of the compaction process, the coalescence of DNA segments covered by bound peptide molecules leads to the formation of DNA loops stabilized by the interaction between peptide molecules bound to different DNA segments. Further increase in the peptide/DNA ratio leads to the formation of rod-like structures each consisting of two or more double-stranded DNA segments. The final stage of the compaction process involves folding of fibrillar macromolecular complexes into a globular structure containing only one DNA molecule.

Base Sequence↗
PubMed1988

[Compounds similar to acyclovir. I. Synthesis of "complete" analogs of nucleosides].

"Full" acyclic analogues of ribonucleosides, 1-(1,2,6-trihydroxy-4-oxahex-3-yl)thymine and -cytosine, 3- and 9-(1,2,6-trihydroxy-4-oxahex-3-yl)adenine, and 9-(1,2,6-trihydroxy-4-oxahex-3-yl)guanine, have been prepared by condensation of silylated nucleo-bases with 1,4,5,6-tetraacetoxy-3-oxahexane in the presence of Lewis acids followed by deacetylation.

Acyclovir↗
PubMed1988

[Compounds similar to acyclovir. II. Synthesis of acyclic analogs of 2'-deoxynucleosides].

Acyclic analogues of nucleosides, viz.9- and 3-(1,6-dihydroxy-4-oxahex-3-yl)adenine, 9-(1,6-dihydroxy-4-oxahex-3-yl)guanine, 1-(1,6-dihydroxy-4-oxahex-3-yl)cytosine and thymine, with C3'-C4' bond of the furanose ring cleaved, have been prepared by condensation of trimethylsilyl derivatives of nucleic acid bases with 1,4,6-triacetoxy-3-oxahexane in the presence of Lewis acids followed by treatment with metanolic ammonia.

Acyclovir↗
PubMed1985

Triple rings: a new type of compact structure of circular DNA.

Complexes of circular superhelical pBR322 DNA with a synthetic tripeptide capable of beta-structure formation (dansylhydrazide trivaline) were studied at different peptide/DNA ratios by electron microscopy. It was shown on rotary-shadowed preparations that peptide binding induces intramolecular DNA condensation and compact ring-shaped particles are formed from fibres 120 A thick. The analysis of the morphology of the ring structures observed at various peptide/DNA ratios as well as contour length measurements enabled us to draw conclusions about the organization of the double-stranded DNA filaments in these structures. It was established that the fibres forming compact rings contain three double-stranded DNA segments closely associated due to DNA-peptide and peptide-peptide interactions. The mechanisms leading to the formation of the triple rings may be important in DNA condensation in vivo.

DNA, Circular↗
PubMed1985

Torus-shaped particles formed due to intermolecular condensation of circular DNA upon interaction with synthetic tripeptide.

The morphology of complexes between relaxed circular plasmid pBR322 DNA and tripeptide L-Val-L-Val-L-Val-NH-NH-Dns (TVP) at different peptide/DNA ratios was studied by electron microscopy. The results show that interaction of TVP with circular DNA leads to the formation of perfect torus-shaped particles. The torus parameter measurements offer the possibility to conclude that DNA condensation observed is of intermolecular nature. On the basis of the analysis of the structures corresponding to the early stages of DNA compaction the model for intermolecular condensation of circular DNA into torus-shaped particles is proposed.

DNA, Circular↗