Bioorganic & medicinal chemistry letters, Oct 30, 2010
Two classes of 1, 4-disubstituted 1, 2, 3-triazoles were synthesized using one-pot reaction of α-... more Two classes of 1, 4-disubstituted 1, 2, 3-triazoles were synthesized using one-pot reaction of α-tosyloxy ketones/α-halo ketones, sodium azide, and terminal alkynes in the presence of aq PEG (1: 1, v/v) using the click chemistry approach and evaluated for Src kinase inhibitory activity. Structure–activity relationship analysis demonstrated that insertion of C6H5–and 4-CH3C6H4–at position 4 for both classes and less bulkier aromatic group at position 1 in class 1 contribute critically to the modest Src inhibition activity (IC50= 32–43μM) of 1, 4- ...
A liver-selective prodrug (3TCSD) of the antiviral drug lamivudine (3TC) was developed and charac... more A liver-selective prodrug (3TCSD) of the antiviral drug lamivudine (3TC) was developed and characterized. 3TC was coupled to dextran (∼ 25 kDa) using a succinate linker, and the in vitro and in vivo behavior of the conjugate was studied using newly developed size-exclusion and reversed-phase analytical methods. Synthesized 3TCSD had a purity of> 99% with a degree of substitution of 6.5 mg of 3TC per 100 mg of the conjugate. Furthermore, the developed assays were precise and accurate in the concentration ...
Novel extended tetrahedral forms of CO 2 have been synthesized recently under high-pressure condi... more Novel extended tetrahedral forms of CO 2 have been synthesized recently under high-pressure conditions. We perform ab initio density functional theory calculations to investigate whether doping with Si can extend the stability range of such tetrahedral forms of CO 2 to ambient ...
The study of simple stochastic games (SSGs) was initiated by Condon for analyzing the computation... more The study of simple stochastic games (SSGs) was initiated by Condon for analyzing the computational power of randomized space-bounded alternating Turing machines. The game is played by two players, MAX and MIN, on a directed multigraph, and when the play terminates at a sink vertex s, MAX wins from MIN a payoff p(s)∈[0,1]. Condon proved that the problem SSG-VALUE—given a
It is being realized that the traditional closed-door and market driven approaches for drug disco... more It is being realized that the traditional closed-door and market driven approaches for drug discovery may not be the best suited model for the diseases of the developing world such as tuberculosis and malaria, because most patients suffering from these diseases have poor paying capacity. To ensure that new drugs are created for patients suffering from these diseases, it is necessary to formulate an alternate paradigm of drug discovery process. The current model constrained by limitations for collaboration and for sharing of resources with confidentiality hampers the opportunities for bringing expertise from diverse fields. These limitations hinder the possibilities of lowering the cost of drug discovery. The Open Source Drug Discovery project initiated by Council of Scientific and Industrial Research, India has adopted an open source model to power wide participation across geographical borders. Open Source Drug Discovery emphasizes integrative science through collaboration, open-sharing, taking up multi-faceted approaches and accruing benefits from advances on different fronts of new drug discovery. Because the open source model is based on community participation, it has the potential to self-sustain continuous development by generating a storehouse of alternatives towards continued pursuit for new drug discovery. Since the inventions are community generated, the new chemical entities developed by Open Source Drug Discovery will be taken up for clinical trial in a non-exclusive manner by participation of multiple companies with majority funding from Open Source Drug Discovery. This will ensure availability of drugs through a lower cost community driven drug discovery process for diseases afflicting people with poor paying capacity. Hopefully what LINUX the World Wide Web have done for the information technology, Open Source Drug Discovery will do for drug discovery.
Natural proteins are concatenated amino acids with definite handedness or chirality, with their s... more Natural proteins are concatenated amino acids with definite handedness or chirality, with their spatial orientation being preferentially left handed or L-chiral. This paper discusses the biophysics of stereo-chemical perturbation to proteins using D-(α) amino acid and its utility as an additional design alphabet while scripting novel protein structures.
Nature is the international weekly journal of science: a magazine style journal that publishes fu... more Nature is the international weekly journal of science: a magazine style journal that publishes full-length research papers in all disciplines of science, as well as News and Views, reviews, news, features, commentaries, web focuses and more ...
Phytocystatins constitute a multigene family that regulates the activity of endogenous and/or exo... more Phytocystatins constitute a multigene family that regulates the activity of endogenous and/or exogenous cysteine proteinases. Cereal crops like wheat are continuously threatened by a multitude of pathogens, therefore cystatins offer to play a pivotal role in deciding the plant response. In order to study the need of having diverse specificities and activities of various cystatins, we conducted comparative analysis of
Bioorganic & medicinal chemistry letters, Oct 30, 2010
Two classes of 1, 4-disubstituted 1, 2, 3-triazoles were synthesized using one-pot reaction of α-... more Two classes of 1, 4-disubstituted 1, 2, 3-triazoles were synthesized using one-pot reaction of α-tosyloxy ketones/α-halo ketones, sodium azide, and terminal alkynes in the presence of aq PEG (1: 1, v/v) using the click chemistry approach and evaluated for Src kinase inhibitory activity. Structure–activity relationship analysis demonstrated that insertion of C6H5–and 4-CH3C6H4–at position 4 for both classes and less bulkier aromatic group at position 1 in class 1 contribute critically to the modest Src inhibition activity (IC50= 32–43μM) of 1, 4- ...
A liver-selective prodrug (3TCSD) of the antiviral drug lamivudine (3TC) was developed and charac... more A liver-selective prodrug (3TCSD) of the antiviral drug lamivudine (3TC) was developed and characterized. 3TC was coupled to dextran (∼ 25 kDa) using a succinate linker, and the in vitro and in vivo behavior of the conjugate was studied using newly developed size-exclusion and reversed-phase analytical methods. Synthesized 3TCSD had a purity of> 99% with a degree of substitution of 6.5 mg of 3TC per 100 mg of the conjugate. Furthermore, the developed assays were precise and accurate in the concentration ...
Novel extended tetrahedral forms of CO 2 have been synthesized recently under high-pressure condi... more Novel extended tetrahedral forms of CO 2 have been synthesized recently under high-pressure conditions. We perform ab initio density functional theory calculations to investigate whether doping with Si can extend the stability range of such tetrahedral forms of CO 2 to ambient ...
The study of simple stochastic games (SSGs) was initiated by Condon for analyzing the computation... more The study of simple stochastic games (SSGs) was initiated by Condon for analyzing the computational power of randomized space-bounded alternating Turing machines. The game is played by two players, MAX and MIN, on a directed multigraph, and when the play terminates at a sink vertex s, MAX wins from MIN a payoff p(s)∈[0,1]. Condon proved that the problem SSG-VALUE—given a
It is being realized that the traditional closed-door and market driven approaches for drug disco... more It is being realized that the traditional closed-door and market driven approaches for drug discovery may not be the best suited model for the diseases of the developing world such as tuberculosis and malaria, because most patients suffering from these diseases have poor paying capacity. To ensure that new drugs are created for patients suffering from these diseases, it is necessary to formulate an alternate paradigm of drug discovery process. The current model constrained by limitations for collaboration and for sharing of resources with confidentiality hampers the opportunities for bringing expertise from diverse fields. These limitations hinder the possibilities of lowering the cost of drug discovery. The Open Source Drug Discovery project initiated by Council of Scientific and Industrial Research, India has adopted an open source model to power wide participation across geographical borders. Open Source Drug Discovery emphasizes integrative science through collaboration, open-sharing, taking up multi-faceted approaches and accruing benefits from advances on different fronts of new drug discovery. Because the open source model is based on community participation, it has the potential to self-sustain continuous development by generating a storehouse of alternatives towards continued pursuit for new drug discovery. Since the inventions are community generated, the new chemical entities developed by Open Source Drug Discovery will be taken up for clinical trial in a non-exclusive manner by participation of multiple companies with majority funding from Open Source Drug Discovery. This will ensure availability of drugs through a lower cost community driven drug discovery process for diseases afflicting people with poor paying capacity. Hopefully what LINUX the World Wide Web have done for the information technology, Open Source Drug Discovery will do for drug discovery.
Natural proteins are concatenated amino acids with definite handedness or chirality, with their s... more Natural proteins are concatenated amino acids with definite handedness or chirality, with their spatial orientation being preferentially left handed or L-chiral. This paper discusses the biophysics of stereo-chemical perturbation to proteins using D-(α) amino acid and its utility as an additional design alphabet while scripting novel protein structures.
Nature is the international weekly journal of science: a magazine style journal that publishes fu... more Nature is the international weekly journal of science: a magazine style journal that publishes full-length research papers in all disciplines of science, as well as News and Views, reviews, news, features, commentaries, web focuses and more ...
Phytocystatins constitute a multigene family that regulates the activity of endogenous and/or exo... more Phytocystatins constitute a multigene family that regulates the activity of endogenous and/or exogenous cysteine proteinases. Cereal crops like wheat are continuously threatened by a multitude of pathogens, therefore cystatins offer to play a pivotal role in deciding the plant response. In order to study the need of having diverse specificities and activities of various cystatins, we conducted comparative analysis of
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