Uterine and placental 5-HT profile in different gestational period of albino rats

Possible role of 5-HT in pregnancy was investigated in albino rats by biological estimation of uterine and placental 5-HT contents in different periods of gestation in normal and drug treated rats. Uterine 5-HT level increased steadily from day-1 of gestation to reach the peak on day-7; thereafter, the level continued to decline throughout the period till day-20 when 5-HT level was lowest. From day-20, a mild secondary rise started and remained persistent even after parturition. The results show that a critical level of 5-HT in early gestational period is necessary for conception. Manipulation of endogenous 5-HT do not influence duration of gestation.     

New facets of larger Nest motifs in proteins

The Nest is a concave-shaped structural motif in proteins formed by consecutive enantiomeric left-handed (L) and right-handed (R) helical conformation of the backbone. This important motif subsumes many turn and helix capping structures and binds electron-rich ligands. Simple Nests are either RL or LR. Larger Nests (>2 residues long) may be RLR, LRL, RLRL, and so forth, being considered as composed of overlapping simple Nests. The larger Nests remain under-explored despite their widely known contributions to protein function. In our study, we address whether the recurrence of enantiomeric geometry in the larger Nests constrains the peptide backbone such that distinct compositional and conformational preferences are seen compared to simple Nests. Our analysis reveals the critical role of the L helical torsion angle in the formation of larger Nests. This can be observed through the higher propensity of residue or secondary structure combinations in LR and LRL backbone conformation in comparison to RL or RLR, although LR/LRL is considerably lower by occurrence. We also find that the most abundant doublets and triplets in Nests have a propensity for particular secondary structures, suggesting a strong sequence-structure relationship in the larger Nest. Overall, our analysis corroborates distinct features of simple and the larger Nests. Such insights would be helpful towards in-vitro design of peptides and peptidomimetic studies.     

Circular Dichroism Studies of the Structure of DNA Complex with Berberine

Abstract

The binding of the benzodioxolo-benzoquinolizine alkaloid, berberine chloride to natural and synthetic DNAs has been studied by intrinsic and extrinsic circular dichroic measurements. Binding of berberine causes changes in the circular dichroism spectrum of DNA as shown by the increase of molar ellipticity of the 270nm band, but with very little change of the 240nm band. The molar ellipticity at the saturation depends strongly on the base composition of DNA and also on salt concentration, but always larger for the AT rich DNA than the GC rich DNA The features in the circular dichroic spectral changes of berberine-synthetic DNA complexes were similar to that of native DNA but depends on the sequence of base pairs.

On binding to DNA and polynucleotides, the alkaloid becomes optically active. The extrinsic circular dichroism developed in the visible absorption region (300–500nm) for the berberine-DNA complexes shows two broad spectral bands in the regions 425–440nm and 340–360nm with the maximum varying depending on base composition and sequence of DNA While the 425nm band shows less variation on the binding ratio, the 360nm band is remarkably dependent on the DNA/alkaloid ratio. The generation of the alkaloid associated extrinsic circular dichroic bands is not dependent on the base composition or sequence of base pairs, but the nature and magnitude of the bands are very much dependent on these two factors and also on the salt concentration. The interpretation of the results with respect to the modes of the alkaloid binding to DNA are presented.     

Design,synthesis and structure–activity relationship of rhenium 2-arylbenzothiazoles as β-amyloid plaque binding agents

To continue our efforts toward the development of ^99mTc PiB analogs, we have synthesized 24 neutral and lipophilic Re (as a surrogate of ^99mTc) 2-arylbenzothiazoles, and explored their structure–activity relationship for binding to Aβ_1–40 fibrils. These Re complexes were designed and synthesized via the integrated approach, so their ^99mTc analogs would have a greater chance of crossing the blood–brain barrier. While the lipophilicities (log P_C18 = 1.59–3.53) of these Re 2-arylbenzothiazoles were all within suitable range, their binding affinities (K_i = 30–617 nM) to Aβ_1–40 fibrils varied widely depending on the selection and integration of the tetradentate chelator into the 2-phenylbenzothiazole pharmacophore. For potential clinical applications, further refinement to obtain Re 2-arylbenzothiazoles with better binding affinities (<10 nM) will likely be needed. The integrated approach reported here to generate compact, neutral and lipophilic Re 2-arylbenzothiazoles could be applied to other potent pharmacophores as well to convert other current Aβ PET tracers to their ^99mTc analogs for more widespread application via the use of SPECT scanners.     

C3′-endo-puckered pyrrolidine containing PNA has favorable geometry for RNA binding: Novel ethano locked PNA (ethano-PNA)

A novel peptide nucleic acid (PNA) analogue is designed with a constraint in the aminoethyl segment of the aegPNA backbone so that the dihedral angle β is restricted within 60–80°, compatible to form PNA:RNA duplexes. The designed monomer is further functionalized with positively charged amino-/guanidino-groups. The appropriately protected monomers were synthesized and incorporated into aegPNA oligomers at predetermined positions and their binding abilities with cDNA and RNA were investigated. A single incorporation of the modified PNA monomer into a 12-mer PNA sequence resulted in stronger binding with complementary RNA over cDNA. No significant changes in the CD signatures of the derived duplexes of modified PNA with complementary RNA were observed.