Contrasting solution conformations of peptides containing α,α-dialkylated residues with linear and cyclic side chains

The conformational properties of α,α-dialkylated amino acid residues possessing acyclic (diethylglycine, Deg: di-n-propylglycine, Dpg; di-n-butylglycine, Dbg) and cyclic (1-amino-cycloalkane-1-carboxylic acid, Acnc) side chains have been compared in solution. The five peptides studied by nmr and CD spectroscopy are Boc-Ala-Xxx-Ala-OMe, where Xxx = Deg(I). Dpg (II), Dbg (III), Ac6c (IV), and Ac7c (V). Delineation of solvent-shielded NH groups have been achieved by solvent and temperature dependence of NH chemical shifts in CDCl3 and (CD3)2SO and by paramagnetic radical induced line broadening in pepiide III. In the Dxg peptides the order of solvent exposure of NH groups is Ala(1) > Ala(3) > Dxg(2), whereas in the Acnc peptides the order of solvent exposure of NH groups is Ala(1) > Acnc(2) > Ala(3). The nmr results suggest that Acnc peptides adopt folded β-turn conformations with Ala(1) and Acnc(2) occupying i + 1 and i + 2 positions. In contrast, the Dxg peptides favor extended C5 conformations. The conformational differences in the two series are clearly borne out in CD studies. The solution conformations of peptides I-III are distinctly different from the β-turn structure observed in crystals. Low temperature nmr spectra recorded immediately after dissolution of crystals of peptide II provide evidence for a structural transition. Introduction of an additional hydrogen-bonding function in Boc-Ala-Dpg-Ala-NHMe (VI) results in a stabilization of a consecutive β-turn or incipient 310-helix in solution

A CLINICAL STUDY OF PATIENTS WITH IDIOPATHIC THROMBOCYTOPENIC PURPURA

OBJECTIVE To study the incidence, age and sex distribution among adults, various modes of presentation, correlation between thrombocytopenia and bleeding manifestations and various modalities of treatment of Idiopathic Thrombocytopenic Purpura in a tertiary care hospital in India.MATERIALS AND METHODSProspective study consisting of 4o cases of ITP admitted to Kasturba Medical College Hospital, Manipal from November 2005 to March 2007. Patients above 14 years of age admitted with thrombocytopenia in this institution were screened based on detailed clinical history, physical examination and laboratory investigations.RESULTSThe maximum incidence was in the 3 rd decade of life accounting for 27.5% of the patients. Ratio of male to female was 1:1.9 with female preponderance. Females in 3 rd decade had maximum incidence while males in 4th decade have maximum incidence. Majority 12 (85.71%) of male patients and 15(57.69%) of female patients  developed purpura during the course of disease. The mean count was 17.8X109/L with range between 2.0 X109/L to 76 X109/L. Cutaneous bleeding spots were found to be assosiated with counts above 25000X109/L and hematuria with lowest counts around 4000 X109/L. 20 (50%) of the above 40 patients responded to corticposteroids alone and did not have any further relapse. Among the remaining patients 3 (7.5%) had a relapse of symptoms within next 6 months and responded to repeat prednisolone started at 1mg/kg. 2 (5%) patients were given steroids tapering dose with IV Immune globulins for initial 5 days as therapy to which they responded.CONCLUSIONIdiopathic thrombocytopenia is 1.9 times more common in females than males. Most common presentation is bleeding spots over body. Bleeding manifestations are more common with thrombocytopenia less than 30000/mm3. Corticosteroids are the mainstay in treatment. Complete remission is seen in up to 57.5% of the patients. Splenectomy is the second modality of treatment in ITP. Complete and sustained remission is seen 75% of patients. Â

Simple expressions for the long walk distance

The walk distances in graphs are defined as the result of appropriate transformations of the $\sum_{k=0}^\infty(tA)^k$ proximity measures, where $A$ is the weighted adjacency matrix of a connected weighted graph and $t$ is a sufficiently small positive parameter. The walk distances are graph-geodetic, moreover, they converge to the shortest path distance and to the so-called long walk distance as the parameter $t$ approaches its limiting values. In this paper, simple expressions for the long walk distance are obtained. They involve the generalized inverse, minors, and inverses of submatrices of the symmetric irreducible singular M-matrix ${\cal L}=\rho I-A,$ where $\rho$ is the Perron root of $A.$Comment: 7 pages. Accepted for publication in Linear Algebra and Its Application

Stereochemistry of linking segments in the design of helix-helix motifs in peptides. Crystallographic comparison of a glycyl- dipropylglycyl-glycyl segment in a tripeptide and a 14-residue peptide

As part of a program to develop synthetic helix–linker–helix peptides the conformational properties of various linking segments are currently being investigated. The propensity of α,α-di-n-propylglycine (Dpg) residues to adopt backbone conformations in the extended region of the Ramachandran map, suggested by theoretical calculations and supported by experimental observations, prompted us to investigate the utility of the Gly-Dpg-Gly segment as a rigid linking motif. The crystal structure of the achiral tripeptide Boc-Gly-Dpg-Gly-OH 1 revealed a fully extended conformation (ϕ = ±178°, ψ = ±171°) at Dpg(2), with Gly(1) adopting a helical conformation (ϕ = +-72 °, ψ = +-32 °). The addition of flanking helical segments in the 14 residue peptide Boc-Val-Val-Ala-Leu-Gly-Dpg-Gly-Val-Ala-Leu-Aib-Val-Ala-Leu-OMe 2 resulted in the crystallographic characterization of a continuous helix over the entire length of the peptide. Peptide 1 crystallized in the centrosymmetric space group P21/c with a = 9.505(2) Å, b = 11.025(2) Å, c = 20.075(4) Å, β = 90.19° and Z = 4. Peptide 2 crystallized in space group P212121 with a = 10.172(1) Å, b = 17.521(4) Å, c = 46.438(12) Å and Z = 4. A comparative analysis of Gly-Dpg-Gly segments from available crystal structures indicates a high conformational variability of this segment. This analysis suggests that context and environment may be strong conformational determinants for the Gly-Dpg-Gly segment

Quantumness of noisy quantum walks: a comparison between measurement-induced disturbance and quantum discord

Noisy quantum walks are studied from the perspective of comparing their quantumness as defined by two popular measures, measurement-induced disturbance (MID) and quantum discord (QD). While the former has an operational definition, unlike the latter, it also tends to overestimate non-classicality because of a lack of optimization over local measurements. Applied to quantum walks, we find that MID, while acting as a loose upper bound on QD, still tends to reflect correctly the trends in the behavior of the latter. However, there are regimes where its behavior is not indicative of non-classicality: in particular, we find an instance where MID increases with the application of noise, where we expect a reduction of quantumness.Comment: 5 pages with 4 figures, Published Versio

Conformational choice at α,α-di-n-propylglycine residues: helical or fully extended structures?

The conformational analysis of peptides containing a single α,α-di-n-propylglycine (Dpg) residue incorporated into valine-rich sequences has been undertaken in order to delineate the possible role of sequence effects in stabilizing fully extended (C5) or local helical conformations at this residue. The three peptides Boc-Val-Dpg-Val-OMe (3), Boc-Val-Val-Dpg-Val-OMe (4), Boc-Val-Val-Dpg-Val-Val-OMe (5), have been studied by 1H-nmr methods in chloroform (CDCl3) and dimethylsulfoxide (DMSO) solutions. Even in a relatively poorly solvating medium like CDCl3, all the valine NH groups appear to be solvent-exposed, suggesting an absence of folded -turn conformations. However, in both CDCl3 and DMSO the Dpg NH groups in all the three peptides appear to behave like apparently solvent-inaccessible groups. In fully extended C5 conformations, the proximity of the NH and CO groups of Dpg may preclude effective solvation due to a combination of stereoelectronic factors. Nuclear Overhauser effects provide support for the largely extended backbones. The crystal structure of peptide 3 reveals an extended conformation at Dpg (2) with Φ= -176°, Ψ = 180°. A correlation between the crystallographically observed backbone conformation and solution nmr parameters in DMSO has been attempted using available data. Dpg residues placed in poor helix stabilizing environments may be expected to favor a local C5 conformation

Context-dependent conformation of diethylglycine residues in peptides

Diethylglycine (Deg) residues incorporated into peptides can stabilize fully extended (C5) or helical conformations. The conformations of three tetrapeptides Boc-Xxx-Deg-Xxx-Deg-OMe (Xxx = Gly, GD4; Leu, LD4 and Pro, PD4) have been investigated by NMR. In the Gly and Leu peptides, NOE data suggest that the local conformations at the Deg residues are fully extended. Low temperature coefficients for the Deg(2) and Deg(4) NH groups are consistent with their inaccessibility to solvent, in a C5 conformation. NMR evidence supports a folded β-turn conformation involving Deg(2)-Gly(3), stabilized by a 4→1 intramolecular hydrogen bond between Pro(1) CO and Deg(4) NH in the proline containing peptide (PD4). The crystal structure of GD4 reveals a hydrated multiple turn conformation with Gly(1)-Deg(2) adopting a distorted type II/II′ conformation, while the Deg(2)-Pro(3) segment adopts a type III/III′ structure. A lone water molecule is inserted into the potential 4 → 1 hydrogen bond of the Gly(1)-Deg(2) β-turn

Village Knowledge Centers and the Use of GIS-derived Products in Enhancing Micro-level Drought Preparedness: a Case study from South Central India

Drought affects hundreds of millions of people in the developing world and causes serious disruption of social and economic activities. Preparedness is better than relief and information is the backbone of drought preparedness. In this paper we report the results from a study in the use of GIS- derived products to assess micro-level drought vulnerability, taking a cluster of 17 villages in the South Central India as the study area. An internet-connected rural information center, linked to village knowledge centers, played a key role in testing the utility of this product, and the associated local-level predictions for seasonal rainfall

Conformation of di-n-propylglycine residues (Dpg) in peptides: Crystal structures of a type I′β-turn forming tetrapeptide and an α-helical tetradecapeptide

The crystal structures of two oligopeptides containing di-n-propylglycine (Dpg) residues, Boc-Gly-Dpg-Gly-Leu-OMe (1) and Boc-Val-Ala-Leu-Dpg-Val-Ala-Leu-Val-Ala-Leu-Dpg-Val-Ala-Leu-OMe (2) are presented. Peptide 1 adopts a type I-turn conformation with Dpg(2)-Gly(3) at the corner positions. The 14-residue peptide 2 crystallizes with two molecules in the asymmetric unit, both of which adopt α-helical conformations stabilized by 11 successive 5 → 1 hydrogen bonds. In addition, a single 4 → 1 hydrogen bond is also observed at the N-terminus. All five Dpg residues adopt backbone torsion angles (φ,ψ) in the helical region of conformational space. Evaluation of the available structural data on Dpg peptides confirm the correlation between backbone bond angle N-Cα-C'(ζ) and the observed backbone φ,ψ, values. For ζ > 106°, helices are observed, while fully extended structures are characterized by ζ < 106°. The mean values for extended and folded conformations for the Dpg residue are 103.6° ± 1.7° and 109.9° ± 2.6°, respectively