Homology modeling based solution structure of Hoxc8-DNA complex: Role of context bases outside TAAT stretch

Published in: Journal, Comparative Study, Article, Volume :22, Issue : 6, Pages : 707-718

DOI : 10.1080/07391102.2005.10507037

Author : Roy, Sujata; Sen, Srikanta

Abstract : The 3D structure of neither Hoxc8 nor Hoxc8-DNA complex is known. The repressor protein Hoxc8 binds to the TAAT stretch of the promoter of the osteopontin gene and modulates its expression. Over expression of the osteopontin gene is related to diseases like osteoporosis, multiple sclerosis, cancer et cetera. In this paper we have proposed a 3D structure of Hoxc8-DNA complex obtained by Homol. modeling and mol. dynamics (MD) simulation in explicit water. The crystal structure (9ant.pdb) of Antennapedia homeodomain in complex with its DNA sequence was chosen as the template based on (i) high sequence identity (85% for the protein and 60% for the DNA) and (ii) the presence of the TAAT stretch in interaction with the protein. The resulting model was refined by MD simulation for 2.0ns in explicit water. This refined model was then characterized in terms of the structural and the interactional features to improve our understanding of the mechanism of Hoxc8-DNA recognition. The interaction pattern shows that the residues Ile195, Gln198, and Asn199, and the bases S2-4TAATG8 are most important for recognition suggesting the stretch TAATG as the ‘true recognition element’ in the present case. A strong and long-lived water bridge connecting Gln198 and the base of S1-C7 complementary to S2-G8 was observed Our predicted model of Hoxc8-DNA complex provides us with features that are consistent with the available exptl. data on Hoxc8 and the general features of other homeodomain-DNA complexes. The predictions based on the model are also amenable to exptl. verification.

DNA topoisomerases in life and death: Implications in kinetoplastid protozoa

Published in: Journal, General Review, Article, Review Volume :4, Issue : 6, Pages : 711-722

DOI : 10.2174/1566524043360302

Author : Chowdhury, Arnab Roy; Majumder, Hemanta K.

Abstract : A review. Current biomedical research has its focus on the search for newer intervention strategies to control public health impact of parasitic diseases. The dramatic advances of mol. and cellular biol. in recent times have provided opportunities for discovering and evaluating mol. targets for drug designing, which now form a rational basis for the development of improved anti parasitic therapy. DNA topoisomerases, the “”cellular magicians”” involved in nearly all biol. processes governing DNA, have emerged as one such biol. target. Over the last 2 decades, interest in topoisomerases has expanded beyond the realm of the basic science laboratory into the clin. arena. This review aims at providing a comprehensive insight into the biol. of DNA topoisomerases and also focuses on its evolution as a drug target in the unicellular kinetoplastids.

2,4-Dinitroimidazole: Microwave assisted synthesis and use in synthesis of 2,3-dihydro-6-nitroimidazo[2,1-b]oxazole analogues with antimycobacterial activity

Published in: Journal, Volume :41, Issue : 1, Pages : 51-55

DOI : 10.1002/jhet.5570410108

Author : Bhaumik, Kankan; Akamanchi, K. G.

Abstract : 2,4-Dinitroimidazole (I), an important starting material for nitroimidazooxazole and nitroimidazooxazine types of antitubercular agents was synthesized by rearrangement of 1,4-dinitroimidazole under microwave irradiation Various new nitroimidazooxazoles analogs were prepared from I and were tested preliminarily against Mycobacterium tuberculosis, H37Rv strain. Some were found to be active.

Solid-phase approach towards the synthesis of functionalized imidazo[1,2-b]pyrazol-2-ones

Published in: Journal, Volume : 45, Issue : 6, Pages : 1275-1277

DOI : 10.1016/j.tetlet.2003.11.135

Author : Blass, Benjamin E.; Srivastava, Anil; Coburn, Keith R.; Faulkner, Amy L.; Janusz, John J.; Ridgeway, James M.; Seibel, William L.

Abstract : The solid-phase synthesis of a series of imidazo[1,2-b]pyrazol-2-ones, an interesting 5,5-fused ring system, based on diverse set of hydrazine acids and malonitriles is described. The method involves formation of 5-aminopyrazoles on solid support and subsequent cyclizative cleavage off the resin. Compounds were obtained in acceptable to excellent yields and are suitable for biol. evaluation without further purification Example compounds thus prepared included 1,8-dihydro-3-[[4-(trifluoromethoxy)phenyl]methyl]-6H-imidazo[1,2-b]thieno[3,4-d]pyrazol-2(3H)-one (I) and 6-(1,1-dimethylethyl)-3-[[4-(trifluoromethoxy)phenyl]methyl]-1H-imidazo[1,2-b]pyrazol-2(3H)-one (II).

Novel Petasis boronic acid reactions with 1,3,5-tri-oxygenated benzenes

Published in: Journal, Volume :44, Issue : 49, Pages : 8861-8863

DOI : 10.1016/j.tetlet.2003.09.178

Author : Naskar, Dinabandhu; Roy, Amrita; Seibel, William L.

Abstract : 1,3,5-Tri-Oxygenated benzenes can serve as substrates for the Petasis boronic acid reaction, providing a practical synthetic route for the two C-C bond formation of α-(1,3,5-tri-oxygenated phenyl)carboxylic acids. The scope and limitations of this method were examined

Hydroxylamines and sulfinamide as amine components in the Petasis boronic acid-Mannich reaction: synthesis of N-hydroxy or alkoxy-α-aminocarboxylic acids and N-(tert-butyl sulfinyl)-α-amino carboxylic acids

Published in: Journal, Volume :44, Issue : 49, Pages : 8865-8868

DOI : 10.1016/j.tetlet.2003.09.179

Author : Naskar, Dinabandhu; Roy, Amrita; Seibel, William L.; Portlock, David E.

Abstract : An efficient synthesis of N-hydroxy or alkoxy-α-aminocarboxylic acids and N-(tert-Bu sulfinyl)-α-amino carboxylic acids was developed from N,O-alkyl or hydroxylamines and tert-Bu sulfinamide utilizing a Petasis boronic acid-Mannich reaction. The scope and limitations of this method were examined

The synthesis of aza-β-lactams via tandem Petasis-Ugi multi-component condensation and 1,3-diisopropylcarbodiimide (DIC) condensation reaction

Published in: Journal, Volume :44, Issue : 33, Pages : 6297-6300

DOI : 10.1016/s0040-4039(03)01524-7

Author : Naskar, Dinabandhu; Roy, Amrita; Seibel, William L.; West, Laura; Portlock, David E.

Abstract : The synthetic utility of a tandem Petasis-Ugi multi-component condensation and 1,3-diisopropylcarbodiimide condensation reactions have been employed to efficiently prepare two to four-dimensional libraries of aza-β-lactams.

Positional isomerization of quinine and quinidine via rhodium on alumina catalysis: practical one-step synthesis of Δ3,10-isoquinine and Δ3,10-isoquinidine

Published in: Journal, Volume : 44, Issue : 28, Pages : 5365-5368

DOI : 10.1016/s0040-4039(03)01180-8

Author : Portlock, David E.; Naskar, Dinabandhu; West, Laura; Seibel, William L.; Gu, Titan; Krauss, Howard J.; Peng, X. Sean; Dybas, Paul M.; Soyke, Edward G.; Ashton, Stephen B.; Burton, Jonathan

Abstract : The synthesis of Δ3,10-isoquinine (5Z,5E) and Δ3,10-isoquinidine (6Z,6E) was achieved in one-step through positional isomerization of the terminal alkene in the parent cinchona alkaloids using catalytic amounts of 5% Rh/Al2O3 and excess hydrochloric acid in refluxing 50% aqueous EtOH. The products were obtained in good yields as a mixture of E and Z geometric isomers and fully characterized using spectroscopic methods.

Solid-phase synthesis of five-dimensional libraries via a tandem Petasis-Ugi multi-component condensation reaction

Published in: Journal, Volume : 44, Issue : 27, Pages : 5121-5124

DOI : 10.1016/s0040-4039(03)01119-5

Author : Portlock, David E.; Naskar, Dinabandhu; West, Laura; Ostaszewski, Ryszard; Chen, Jack J.

Abstract : Five-dimensional libraries of dipeptide amides are readily prepared using a solid-phase tandem Petasis-Ugi multi-component condensation protocol on either a RINK amine or Universal RINK isonitrile resin. The method is practical and can be automated to prepare a large number of compounds useful for high throughput biol. screening.

A tandem Petasis-Ugi multi component condensation reaction: solution phase synthesis of six dimensional libraries

Published in: Journal, Volume : 44, Issue : 3, Pages : 603-605

DOI : 10.1016/s0040-4039(02)02619-9

Author : Portlock, David E.; Ostaszewski, Ryszard; Naskar, Dinabandhu; West, Laura

Abstract : Amino acids with three points of diversity generated from the Petasis boronic acid-Mannich reaction can be used as one of the four components of the Ugi condensation to prepare six dimensional libraries of dipeptide amides. Thus, petasis amino acid substrate Me2NCH2CO2H underwent Ugi reaction with p-MeC6H4CH2NH2, PhCH2CH2CHO, and 2,6-Me2C6H3NC to afford 42% Me2NCH2CON(CH2C6H4Me-p)CH(CH2CH2Ph)CONHC6H3Me2-2,6.