Genome subtraction for novel target definition in Salmonella typhi

Large genomic sequencing projects of pathogens as well as human genome leads to immense genomic and proteomic data which would be very beneficial for the novel target identification in pathogens. Subtractive genomic approach is one of the most useful strategies helpful in identification of potential targets. The approach works by subtracting the genes or proteins homologous to both host and the pathogen and identify those set of gene or proteins which are essential for the pathogen and are exclusively present in the pathogen. Subtractive genomic approach is employed to identify novel target in salmonella typhi. The pathogen has 4718 proteins out of which 300 are found to be essential (“ indispensable to support cellular life”) in the pathogen with no human homolog. Metabolic pathway analyses of these 300 essential proteins revealed that 149 proteins are exclusively involved in several metabolic pathway of S. typhi. 8 metabolic pathways are found to be present exclusively in the pathogen comprising of 27 enzymes unique to the pathogen. Thus, these 27 proteins may serve as prospective drug targets. Sub-cellular localization prediction of the 300 essential proteins was done which reveals that 11 proteins lie on the outer membrane of the pathogen which could be probable vaccine candidates.     

Anilide tertiary carbinols: A new structural class of potent potassium channel openers

A new structural class of anilide tertiary carbinol potassium channel openers (PCOs) is described.     

Synthetic glucagon antagonists and partial agonists.

This paper reports the synthesis and the biological activities of six new glucagon analogues. In these compounds N-terminal modifications of the glucagon sequence were made, in most cases combined with changes in the C-terminal region which had been shown previously to enhance receptor affinity. The design of these analogues was based on [Lys17,18,Glu21]glucagon,1 a superagonist, which binds five times better than glucagon to the glucagon receptor, and on the potent glucagon antagonist [D-Phe4,Tyr5,Arg12]glucagon, which does not stimulate adenylate cyclase system even at very high concentrations. The N-terminal modifications involved substitution of His1 by the unnatural conformationally constrained residue, 4,5,6,7-tetrahydro-1H-imidazo[c]pyridine-6-carboxylic acid (Tip) and by desaminohistidine (dHis). In addition we prepared two analogues (6 and 7), in which we deleted the Phe6 residue, which was suggested to be part of a hydrophobic patch and involved in receptor binding. The following compounds were synthesized: [Tip1, Lys17,18,Glu21]glucagon (2); [Tip1,D-Phe4,Tyr5,Arg12,Lys17,18,Glu21]glucagon (3); [dHis1,D-Phe4,Tyr5,Arg12,Lys17,18,Glu21]glucagon (4); [dHis1,Asp3,D-Phe4,Tyr5,Arg12,Lys17,18,Glu21+ ++]glucagon (5); des-Phe6-[Tip1,D-Phe4,Tyr5,Arg12,Glu21]glucagon (6); des-Phe6-[Asp3,D-Phe4,Tyr5,Arg12,Glu21]glucagon (7). The binding potencies of these new analogues relative to glucagon (= 100) are 3.2 (2), 2.9 (3), 10.0 (4), 1.0 (5), 8.5 (6), and 1.7 (7). Analogue 2 is a partial agonist (maximum stimulation of adenylate cyclase (AC) approximately 15% and a potency 8.9% that of glucagon, while the remaining compounds 3-7 are antagonists unable to activate the AC system even at concentrations as high as 10(-5) M. In addition, in competition experiments, analogues 3-7 caused a right-shift of the glucagon stimulated adenylate cyclase dose-response curve.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cytological studies in some species of Momordica

In the genus Momordica three species M. charantia, M. balsamina and M. dioica, have been cytologically investigated. M. dioica has a more asymmetrical karyotype than the other two species.Meiosis in the three species is regular. The strictly monoecious M. charantia and M. balsamina show similarity in the range and frequency of bivalents and chiasmata, whereas M. dioica, a dioecious species, has fewer half chiasmata per chromosome. The evolutionary significance of perennial and annual habits along with allogamous and autogamous breeding systems is discussed. The incompatibility between 2n=22 and 2n=28 species in this genus is strongly indicated by the negative results of crossings between M. charantia and M. balsamina on one side and M. dioica on the other. The possible origin of M. dioica from M. charantia is discussed.This research has been financed in part by a grant made by the United States Department of Agriculture under PL 480.     

Annual cycle of energy allocation to growth and reproduction of yellow perch

Growth (length, weight) of yellow perch Perca flavescens in western and west-central Lake Erie began between June and July, possibly reaching asymptotic size by early winter. Energy density (kJ g⁻¹) of somatic tissue increased markedly from June to September, then declined to low levels by the following spring. Consequently, energy mass (kJ) of somatic tissue increased to September and then declined slowly until March. Ovarian growth began in October, and the size of the ovaries was maximal in April, just before spawning in May. The energy density of ovaries, however, increased to a peak in December, and then declined. The increase in ovary size in the winter, therefore, resulted largely from an allocation of tissue of low energy density. Fecundity and gonad size were correlated with somatic and gonadal energy density. A bioenergetics model was used to describe the monthly allocations of energy to respiration, growth, excretion, and reproduction. Most direct reproductive costs (80%) were incurred from September to December, corresponding to the cycle in the activity of the liver. Energy acquired in the early summer may be critical for determining maturation, fecundity, and egg quality. From 1978 to 1990, <80% of the females from the western and west-central basins of Lake Erie were classed as spent in July.     

Synthesis and sar study of novel CCK-B antagonists

The structure activity relationship and an efficient synthesis of N,N-disubstituted amides of -methyltryptophan via stable oxazolone derivatives 12a and 12b are described.