Molecular modeling of neurokinin B and tachykinin NK₃ receptor complex

The tachykinin receptor NK? is a member of the rhodopsin family of G-protein coupled receptors. The NK? receptor has been regarded as an important drug target due to diverse physiological functions and its possible role in the pathophysiology of psychiatric disorders, including schizophrenia. The NK3 receptor is primarily activated by the tachykinin peptide hormone neurokinin B (NKB) which is the most potent natural agonist for the NK? receptor. NKB has been reported to play a vital role in the normal human reproduction pathway and in potentially life threatening diseases such as pre-eclampsia and as a neuroprotective agent in the case of neurodegenerative diseases. Agonist binding to the receptor is a critical event in initiating signaling, and therefore a characterization of the structural features of the agonists can reveal the molecular basis of receptor activation and help in rational design of novel therapeutics. In this study a molecular model for the interaction of the primary ligand NKB with its G-protein coupled receptor NK? has been developed. A three-dimensional model for the NK? receptor has been generated by homology modeling using rhodopsin as a template. A knowledge based docking of the NMR derived bioactive conformation of NKB to the receptor has been performed utilizing limited ligand binding data obtained from photoaffinity labeling and site-directed mutagenesis studies. A molecular model for the NKB-NK? receptor complex obtained sheds light on the topographical features of the binding pocket of the receptor and provides insight into the biochemical data currently available for the receptor.     

Blocks and modules for Whittaker pairs

Inspired by recent activities on Whittaker modules over various (Lie) algebras, we describe a general framework for the study of Lie algebra modules locally finite over a subalgebra. As a special case, we obtain a very general set-up for the study of Whittaker modules, which includes, in particular, Lie algebras with triangular decomposition and simple Lie algebras of Cartan type. We describe some basic properties of Whittaker modules, including a block decomposition of the category of Whittaker modules and certain properties of simple Whittaker modules under some rather mild assumptions. We establish a connection between our general set-up and the general set-up of Harish-Chandra subalgebras in the sense of Drozd, Futorny and Ovsienko. For Lie algebras with triangular decomposition, we construct a family of simple Whittaker modules (roughly depending on the choice of a pair of weights in the dual of the Cartan subalgebra), describe their annihilators, and formulate several classification conjectures. In particular, we construct some new simple Whittaker modules for the Virasoro algebra. Finally, we construct a series of simple Whittaker modules for the Lie algebra of derivations of the polynomial algebra, and consider several finite-dimensional examples, where we study the category of Whittaker modules over solvable Lie algebras and their relation to Koszul algebras.     

Straightforward copper-catalyzed synthesis of pyrrolopyrazoles from halogenated pyrazolecarbaldehydes

Straightforward synthesis of a variety of pyrrolo-fused pyrazoles via a cascade reaction between halopyrazolecarbaldehydes and ethylisocyanoacetate in the presence of copper and a base is described.     

NaNO2/I2 as an alternative reagent for the synthesis of 1,2,3-benzotriazin-4(3H)-ones from 2-aminobenzamides

An efficient transformation of 2-aminobenzamides to 1,2,3-benzotriazin-4(3H)-ones in the presence of sodium nitrite (NaNO₂) and Iodine (I₂) is described. The reaction is proposed to proceed via formation of nitrosyl halide that induces nitrosylation of the amino group of 2-aminobenzamide leading to diazotization followed by intramolecular cyclization.     

Synthesis,characterization, and biological activity of organophosphates derived from substituted benzoxazole

The reaction of phosphorus oxychlo‐ ride/phosphorus thiochloride with 2‐(2′‐mercapto‐ phenyl)benzoxazole in 1:1, 1:2, and 1:3 molar ratio in the presence of stoichiometric amounts of triethyl‐ amine has afforded a series of organophosphates. These organophosphates have been characterized by elemental analyses, infrared, ¹H NMR, ³¹P NMR, and mass spectral studies. The antifungal activity of these organophosphates has been evaluated against pathogenic fungi Aspergillus niger and Fusarium oxysporium. The antifungal screening data reveal that these compounds are more fungitoxic than 2‐(2′‐mercaptophenyl) benzoxazole. These organophosphates were also found to be insecticidal when tested against Periplenata americana.© 2009 Wiley Periodicals, Inc. Heteroatom Chem 20:309–315, 2009; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20551     

Calculation of the minimum energy conformation of biomolecules by using a global optimization technique. V. Preferred conformations of the thyrotropin-releasing hormone

The preferred conformations of the thyrotropin-releasing hormone (TRH) have been calculated by the global optimization method proposed earlier by us. [G. Subba Rao, R. S. Tyagi, and R. K. Mishra, J. Theor. Biol. 90 , 377 (1981)]. The potential function used comprises the electrostatic, nonbonded, torsional and hydrogen-bonding terms. The results are in good agreement with the crystal structures of TRH. No intramolecular hydrogen bonding is found to occur.     

A parametric algorithm for convex cost network flow and related problems

The convex cost network flow problem is to determine the minimum cost flow in a network when cost of flow over each arc is given by a piecewise linear convex function. In this paper, we develop a parametric algorithm for the convex cost network flow problem. We define the concept of optimum basis structure for the convex cost network flow problem. The optimum basis structure is then used to parametrize v, the flow to be transsshipped from source to sink. The resulting algorithm successively augments the flow on the shortest paths from source to sink which are implicitly enumerated by the algorithm. The algorithm is shown to be polynomially bounded. Computational results are presented to demonstrate the efficiency of the algorithm in solving large size problems. We also show how this algorithm can be used to (i) obtain the project cost curve of a CPM network with convex time-cost tradeoff functions; (ii) determine maximum flow in a network with concave gain functions; (iii) determine optimum capacity expansion of a network having convex arc capacity expansion costs.     

Minimal quadratic residue cyclic codes of lengthp n(p odd prime)

The explicit expressions for the 2n + 1 primitive idempotents in $R_{p^ - } = F[x]/< x^{p^ - } - 1 > $ , whereF is the field of prime power orderq and the multiplicative order ofq modulop ⁿ is ?(p ⁿ)/2 (n ≥ 1 andp is an odd prime), are obtained. An algorithm for computing the generating polynomials of the minimal QR cyclic codes of lengthp ⁿ, generated by these primitive idempotents, is given and hence some bounds on the minimum distance of some QR codes of prime length overGF(q)(q = 2, 3, ...) are obtained.     

Binding energy of triton and scattering lengths in neutron-deuteron collision in Faddeev formalism with local potential

A separable representation for the off-shell two-body t-matrix for a local Hulthén potential is presented, in which deuteron states are chosen as the expansion bases. Using the Faddeev equations with these t-matrices as input, the ground state energy of the triton and doublet and quartet scattering lengths in neutron-deuteron scattering, have been computed. The results have been compared with the experimental findings and the theoretical results of Sitenko et al. obtained in the Sturmian function representation with the same Hulthén potential.