India Peptides Rserach Papers

21. Mar Drugs. 2010 Aug 19;8(8):2384-94.

Total synthesis and antimicrobial activity of a natural cycloheptapeptide of
marine origin.

Dahiya R, Gautam H.

Department of Pharmaceutical Chemistry, NRI Institute of Pharmacy, Bhopal 462
021, Madhya Pradesh, India. rajivdahiya77@rediffmail.com

The present study deals with the first total synthesis of the proline-rich
cyclopolypeptide stylisin 2 via a solution phase technique by coupling of the
Boc-L-Pro-L-Ile-L-Pro-OH tripeptide unit with the L-Phe-L-Pro-L-Pro-L-Tyr-OMe
tetrapeptide unit, followed by cyclization of the resulting linear heptapeptide
fragment. The chemical structure of the finally synthesized peptide was
elucidated by FTIR, ¹H/¹³C-NMR and FAB MS spectral data, as well as elemental
analyses. The newly synthesized peptide was subjected to antimicrobial screening
against eight pathogenic microbes and found to exhibit potent antimicrobial
activity against Pseudomonas aeruginosa, Klebsiella pneumoniae and Candida
albicans, in addition to moderate antidermatophyte activity against pathogenic
Trichophyton mentagrophytes and Microsporum audouinii when compared to standard
drugs--gatifloxacin and griseofulvin.


PMCID: PMC2953409
PMID: 20948913 [PubMed - in process]


22. Chemistry. 2010 Oct 13. [Epub ahead of print]

Short-Peptide-Based Hydrogel: A Template for the In Situ Synthesis of Fluorescent
Silver Nanoclusters by Using Sunlight.

Adhikari B, Banerjee A.

Department of Biological Chemistry, Indian Association for the Cultivation of
Science, Jadavpur, Kolkata, 700 032 (India), Fax: (+91) 332473-2805.

N-terminally Fmoc-protected dipeptide, Fmoc-Val-Asp-OH, forms a transparent,
stable hydrogel with a minimum gelation concentration of 0.2 % w/v. The gelation
property of the hydrogel was investigated by using methods such as transmission
electron microscopy, field-emission scanning electron microscopy, atomic force
microscopy and Fourier transform infrared spectroscopy. The
silver-ion-encapsulating hydrogel can efficiently and spontaneously produce
fluorescent silver nanoclusters under sunlight at physiological pH (7.46) by
using a green chemistry approach. Interestingly, in the absence of any
conventional reducing agent but in the presence of sunlight, silver ions were
reduced by the carboxylate group of a gelator peptide that contains an aspartic
acid residue. These clusters were investigated by using UV/Vis spectroscopy,
photoluminescence spectroscopy, high-resolution transmission electron microscopy
(HR-TEM), atomic force microscopy (AFM) and X-ray diffraction (XRD) studies. Mass
spectrometric analysis shows the presence of a few atoms in nanoclusters
containing only Ag(2). The reported fluorescent Ag nanoclusters show excellent
optical properties, including a very narrow emission profile and large Stokes
shift (>100 nm). The reported fluorescent Ag nanoclusters within hydrogel are
very stable even after 6 months storage in the dark at 4 °C. The as-prepared
hydrogel-nanocluster conjugate could have applications in antibacterial
preparations, bioimaging and other purposes.


PMID: 20945315 [PubMed - as supplied by publisher]


23. Fungal Biol. 2010 Sep;114(9):731-8. Epub 2010 Jun 19.

Molecular and structural characterization of GTP-cyclohydrolase II in
Eremothecium ashbyi NRRL Y-1363: cDNA cloning, comparative sequence analysis and
molecular modeling.

Sengupta S, Chandra TS.

Department of Biotechnology, Indian Institute of Technology Madras, Chennai 600
036, India.

GTP-cyclohydrolase II (GCH II) encoded by RIB1 gene catalyzes the first committed
step in the riboflavin biosynthetic pathway. We report here the cloning and
characterization of the entire RIB1 ORF (EaRIB1) of 942bp by reverse
transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA
ends (RACE-PCR) in Eremothecium ashbyi where it was found to be present as a
single-copy gene. EaRIB1 sequence is available at the GenBank Accession Number
EF565374. The putative peptide of 313-aa has a high similarity of 60-70% with GCH
II sequences from other ascomycete fungi. Gene expression and alignment studies
confirmed the functional annotation of this gene. Homology model was developed
with Escherichia coli (PDB 2BZ1) as template to identify the catalytic domains
and to explore its functional architecture. We report here the first
three-dimensional model of any fungal GCH II which due to its absence in humans
assumes significance for anti-fungal drug targeting.


PMID: 20943182 [PubMed - in process]


24. Expert Opin Ther Targets. 2010 Nov;14(11):1177-97.

Novel drug targets based on metallobiology of Alzheimer's disease.

Bandyopadhyay S, Huang X, Lahiri DK, Rogers JT.

Indian Institute of Toxicology Research, Lucknow, India. sanghmitra@iitr.res.in

IMPORTANCE OF THE FIELD: Increased localization of Zn, Fe, Cu and Al within the
senile plaques (SP) exacerbates amyloid beta (Aβ)-mediated oxidative damage, and
acts as catalyst for Aβ aggregation in Alzheimer's disease (AD). Thus, disruption
of aberrant metal-peptide interactions via chelation therapy holds considerable
promise as a rational therapeutic strategy against Alzheimer's amyloid
pathogenesis. AREAS COVERED IN THIS REVIEW: The complexities of metal-induced
genesis of SP are reviewed. The recent advances in the molecular mechanism of
action of metal chelating agents are discussed with critical assessment of their
potential to become drugs. WHAT THE READER WILL GAIN: Taking into consideration
the interaction of metals with the metal-responsive elements on the Alzheimer's
amyloid precursor protein (APP), readers will gain understanding of several
points to bear in mind when developing a screening campaign for AD-therapeutics.
TAKE HOME MESSAGE: A functional iron-responsive element (IRE) RNA stem loop in
the 5' untranslated region (UTR) of the APP transcript regulates neural APP
translation. Desferrioxamine, clioquinol, tetrathiolmolybdate,
dimercaptopropanol, VK-28, and natural antioxidants, such as curcumin and ginko
biloba need critical evaluation as AD therapeutics. There is a necessity for
novel screens (related to metallobiology) to identify therapeutics effective in
AD.


PMID: 20942746 [PubMed - in process]


25. Folia Microbiol (Praha). 2010 Sep;55(5):520-7. Epub 2010 Oct 13.

Peptides representing the specific variable regions but not the full porin
proteins can be useful for antibody based diagnosis of typhoid fever.

Kumar S, Kapil S, Gautam V, Verma SK, Ray P.

Defence Research and Development Establishment, Division of Microbiology, Gwalior
474 002, India. subodh@drde.drdo.in

Antibody response to major porin proteins of S. Typhi (OmpC and OmpF) was
evaluated in sera of typhoid patients (culture positive, n = 28; Widal positive,
n = 16). Sera from fever patients (n = 6) having etiology other than Salmonella,
and normal healthy human controls (n = 18) were also included. No significant
difference between the anti-OmpC and anti-OmpF antibodies (Ab) of typhoid
patients and controls was observed. The amino acid sequences of OmpC (and OmpF)
porin of enterobacteria was aligned and searched for the variable regions
specific to S. Typhi. Two regions, each representing one specific variable region
of OmpC and OmpF, were selected (peptides for these regions were custom
synthesized). The peptides were evaluated for Ab response of sera. A
significantly higher level of Ab to both the peptides was observed in the sera of
typhoid patients. The findings suggest that porins of S. Typhi are cross reactive
and are not good markers for Ab-based diagnosis of typhoid fever, however,
peptides representing the variable regions specific to S. Typhi may have greater
diagnostic potential.


PMID: 20941590 [PubMed - in process]


26. Oncol Res. 2010;18(11-12):549-59.

Expression of the major fas family and Bcl-2 family of proteins in epithelial
ovarian cancer (EOC) and their correlation to chemotherapeutic response and
outcome.

Chaudhry P, Srinivasan R, Patel FD.

Department of Radiotherapy, Postgraduate Institute of Medical Education and
Research, Chandigarh, India.

Platinum-based chemotherapeutic drugs trigger apoptosis, and deregulation of
apoptotic pathways may contribute to chemoresistance. We investigated the role of
major Fas and Bcl-2 family members as predictors of response to platinum-based
chemotherapy in epithelial ovarian cancer (EOC). The expression of Fas, FasL,
FAP-1, Bax, Bcl-2, and Bcl-X(L) was analyzed in 35 women with EOC at the
transcript level by semiquantitative RT-PCR and at the protein level by
immunohistochemistry. The apoptotic index was determined by TUNEL assay. The
response to chemotherapy was documented and at the end of six cycles of
chemotherapy. Based on their response, two groups were identified: primary
chemosensitive (n = 20) and primary chemoresistant (n = 15). Further, after a
follow-up of 12-46 months, two groups were identified: no evidence of disease (n
= 10) and evidence of disease (n = 25). The primary chemoresistant tumors in
comparison to the chemosensitive tumors had significantly lower levels of Fas
transcript (p = 0.026), Bax transcript (p = 0.042) and Bcl-2 protein (p = 0.038)
and higher levels of Bcl-X(L) (p = 0.040). The apoptotic index revealed a
significant inverse correlation only with Bcl-X(L) protein levels (p = 0.003).
Patients with evidence of disease at last follow-up in comparison to those with
no evidence of disease showed lower Bax transcript (p = 0.012), Bcl-2 protein (p
= 0.014) and lower apoptotic index (p = 0.005) and higher Bcl-X(L) protein levels
(p = 0.023). In conclusion, Bcl-2 family members and apoptotic index are useful
in prediction of response to chemotherapy in EOC. These initial observations need
to be validated in large-scale studies.


PMID: 20939431 [PubMed - indexed for MEDLINE]


27. Appl Biochem Biotechnol. 2010 Oct 13. [Epub ahead of print]

Proline-Specific Extracellular Aminopeptidase Purified from Streptomyces
lavendulae.

Nandan A, Pandey A, Nampoothiri KM.

Biotechnology Division, National Institute for Interdisciplinary Science and
Technology (NIIST), CSIR, Trivandrum, Thiruvananthapuram, 695 019, Kerala, India.

Aminopeptidases catalyze the cleavage of specific amino acids from the amino
terminus of protein or peptide substrates. A proline-specific aminopeptidase was
purified to homogeneity from the culture-free extract of Streptomyces lavendulae
ATCC 14162 in sequential steps comprising ammonium sulfate precipitation,
ultra-filtration, and column chromatography on Q-sepharose and Sephadex G-100.
The purified protein showed approximately 60 kDa in SDS-PAGE and was optimally
active at pH 6.5 and 40 °C. Kinetic studies showed a K (m) and V (max) of 0.23 mM
and 0.087 μmol/min, respectively, using Pro-p-NA, the substrate with maximum
specificity. Enzyme activity was inhibited by PMSF and ions like Zn(2+), Co(2+),
and Ni(2+). However, unlike other aminopeptidases, the activity was enhanced in
the presence of DTT, 1,10-phenanthroline, EDTA, amastatin, and bestatin. Ions
like Ca(2+), Mg(2+), and Mn(2+) also enhanced the activity.


PMID: 20938753 [PubMed - as supplied by publisher]


28. Biochim Biophys Acta. 2010 Oct 16. [Epub ahead of print]

NMR evidence of GM1-induced conformational change of Substance P using isotropic
bicelles.

Gayen A, Goswami SK, Mukhopadhyay C.

Department of Chemistry, University of Calcutta, 92 APC Road, Kolkata 700009,
India.

Substance P (SP) is one of the target neurotransmitters associated with diseases
related to chronic inflammation, pain and depression. The selective receptor for
SP, NK(1)R is located in the heterogeneous microdomains or caveolae in membrane.
Gangliosides, specifically GM1, are markers of these heterogeneous sites. Also,
gangliosides are considered as important regulatory elements in cell-cell
recognition and cell signaling. In the present work, we describe the
conformations of Substance P in the presence of ternary membrane systems
containing GM1 at the physiological concentration. SP is mostly unstructured in
water, but appears as extended 3(10) helical or turn III in isotropic bicelles,
more pronounced in the presence of GM1. NMR results suggest that, in the GM1
containing bicelles, the peptide is more inserted into the membrane with its
C-terminus, while N-terminus lies close to the membrane-water interface. The
NMR-derived conformation of SP in GM1 bicelles is docked on homology modeled
NK(1)R and resulting interactions satisfy reported mutagenesis, fluorescence,
photo-affinity labeling and modeling data. The results highlight efficacy of GM1
in membrane in providing structure in an otherwise flexible neurotransmitter
Substance P; thus providing indication that it may be useful also for other
neurotransmitter peptides/proteins associated with membrane.


PMID: 20937248 [PubMed - as supplied by publisher]


29. Protein Pept Lett. 2010 Nov 12. [Epub ahead of print]

Analysis of the Conformations Corresponding to Hexapeptide and Large Sequences
Characterized by Continuous Single Amino Acid Repeats in Proteins.

Gayatri M, Guruprasad K.

Bioinformatics, Centre for Cellular and Molecular Biology (CCMB), Uppal Road,
Hyderabad - 500 007, India. kunchur.guruprasad@gmail.com.

The analysis of conformations corresponding to continuous amino acid repeat
peptides (CARPs) comprising six or more residues in proteins of known
three-dimensional structure revealed that alanine, glycine, glutamic acid,
proline, valine, histidine, aspartic acid, glutamine and lysine were associated
as repeating amino acid residues. Alanine, glycine and histidine CARPs were most
common, although the histidine hexapeptide and large CARPs mainly correspond to
affinity tags and are not part of the native protein sequence. The Ala and Glu
CARPs were observed either as part of helix, or coil or a combination of these
conformations. The octapeptide Ala CARP in six-hairpin glycosidases was observed
as part of strand and coil conformation. The Gly and Pro CARPs were mainly
associated with coil conformation. Majority of the coil regions in CARPs
contained beta and gamma-turn structural motifs. The conformations of the Asp,
Glu and Lys hexapeptide or larger CARPs were not defined in the corresponding
protein three-dimensional structures analyzed. The longest CARP of known
conformation was observed for alanine as a decapeptide in a lysozyme-like protein
that corresponds to helix. A feature of CARPs is that a majority are exposed to
solvent with accessible surface area greater than 200 Å(2) units in the protein
three-dimensional structure.


PMID: 20937037 [PubMed - as supplied by publisher]


30. Mini Rev Med Chem. 2010 Nov 12. [Epub ahead of print]

Substituted Benzimidazole Derivatives as Angiotensin II -AT1 Receptor Antagonist:
A Review.

Vyas VK, Ghate M.

Department of Pharmaceutical, Chemistry, Institute of Pharmacy, Nirma University,
S.G. Highway, Chharodi, Ahmedabad, 382 481, Gujarat, India. vicky_1744@yahoo.com.

The renin angiotensin system (RAS) plays an important role in regulation of blood
pressure and fluidelectrolyte homeostasis. The renin-angiotensin system consists
of a cascade of enzymatic reactions producing angiotensin II (Ang II). Ang II is
a vasoconstrictive peptide hormone that exerts a wide variety of physiological
actions on cardiovascular, renal, endocrine and central nervous systems. The RAS
can be inhibited at various points to control pathogenesis of hypertension. Renin
inhibitors and angiotensin-converting enzyme (ACE) inhibitors were the earliest
RAS blocking agents. A relatively new class of compounds known as Ang II receptor
antagonists (SARTANs) is developed for the treatment of hypertension. They exert
their action by blocking the binding of Ang II on AT1 receptor. Angiotensin
converting enzyme (ACE) inhibitors are associated with incident of side effects
such as cough and angioedema while clinical trials with Ang II receptor
antagonists have confirmed that these drugs are safe and efficacious for the
treatment of hypertension. Based upon the understanding of molecular interaction
of Ang II receptor antagonists with AT1 receptor some of the common structural
features have been identified, such as a heterocyclic (nitrogen atom) ring
system, an alkyl side chain and an acidic tetrazole group. Research efforts for
development of new molecules with similar structural features have led to the
discovery of various non-peptidic Ang II receptor antagonists with different
substituted heterocylic such as imidazole (losartan) and benzimidazole
(candesartan and telmisaratn). In this study we have critically reviewed various
benzimidazole substituted compounds as Ang II- AT1 receptor antagonists and
explored other potential clinical uses for this class of compounds.


PMID: 20937029 [PubMed - as supplied by publisher]


31. Peptides. 2010 Oct 8. [Epub ahead of print]

Development of peptide and protein nanotherapeutics by nanoencapsulation and
nanobioconjugation.

Yadav SC, Kumari A, Yadav R.

Nanobiology Lab, Biotechnology Division, Institute of Himalayan Bioresource
Technology, Council of Scientific and Industrial Research, Palampur 176061 HP
India.

The targeted delivery of therapeutic peptide by nanocarriers systems requires the
knowledge of interactions of nanomaterials with the biological environment,
peptide release, and stability of therapeutic peptides. Therapeutic application
of nanoencapsulated peptides are increasing exponentially and >1000 peptides in
nanoencapsulated form are in different clinical/trial phase. This review covers
current scenario of therapeutic protein and peptides encapsulation on polymer to
metallic nanocarriers including methods of protein encapsulation, peptide
bioconjugation on nanoparticles, stability enhancement of encapsulated proteins
and its biomedical applications.


PMID: 20934475 [PubMed - as supplied by publisher]


32. J Environ Pathol Toxicol Oncol. 2010;29(2):113-25.

Diallyl disulfide induces caspase-dependent apoptosis via mitochondria-mediated
intrinsic pathway in B16F-10 melanoma cells by up-regulating p53, caspase-3 and
down-regulating pro-inflammatory cytokines and nuclear factor-κβ-mediated Bcl-2
activation.

Pratheeshkumar P, Thejass P, Kutan G.

Amala Cancer Research Centre, Amala Nagar, Thrissur-680555, Kerala State, India.

Diallyl disulfide (DADS) is a major organo-sulfur compound derived from garlic
(Allium sativum), which inhibits the proliferation of various types of cancer
cells. In this study we investigated the effect of DADS on the induction of
apoptosis, as well as its regulatory effect on the activation of transcription
factors in B16F-10 melanoma cells. Treatment of B16F-10 cells with nontoxic
concentrations of DADS resulted in the presence of apoptotic bodies and induced
DNA fragmentation in a dose-dependent manner. Cell-cycle analysis revealed that
the occurrence of the sub-G1 peak was significantly elevated in DADS-treated
cells. DADS treatment also down-reguated Bcl-2 expression and up-regulated p53,
caspase-9, and caspase-3 expression in B16F-10 melanoma cells. The study also
reveals that DADS inhibited the activation and nuclear translocation of p65, p50,
and c-Rel subunits of nuclear factor (NF)-B and other transcription factors, such
as c-fos, activated transcription factor-2, and cyclic adenosine monophosphate
response element-binding protein, in B16F-10 melanoma cells The pro-inflammatory
cytokine production and gene expression of tumor necrosis factor (TNF)-α,
interleukin (IL)-1β, IL-6, and granulocyte-macrophage colony-stimulating factor
(GM-CSF) were down-regulated in DADS-treated cells compared with control B16F-10
metastatic melanoma cells. DADS induces caspase-dependent apoptosis through a
mitochondria-mediated intrinsic pathway in B16F-10 melanoma cells by activating
p53 and caspase-3 gene expression and suppressing pro-inflammatory cytokines and
NF-B-mediated Bcl-2 activation.


PMID: 20932246 [PubMed - indexed for MEDLINE]


33. J Environ Pathol Toxicol Oncol. 2010;29(2):101-11.

Protective effect of Alstonia scholaris against radiation-induced clastogenic and
biochemical alterations in mice.

Jahan S, Goyal PK.

Radiation and Cancer Biology Laboratory, Department of Zoology, University of
Rajasthan, Jaipur, India.

We studied the radioprotective effect of Alstonia scholaris bark extract (ASE) on
cytogenetic alterations in the form of chromosomal aberrations and micronuclei
induction in bone marrow. For this purpose, one group of male Swiss albino mice
was exposed to 2.5 Gy gamma radiation to serve as the irradiated control, while
the other group received ASE (100 mg/kg bwt/d) orally for 5 consecutive days 30
min before irradiation to serve as the experimental group. Results indicated that
dicentrics and chromosomal exchanges were increased at 12 h post-exposure in both
groups, followed by a gradual decline and then disappearance by d 15 and 7,
respectively. However, the occurrence of chromatid breaks and acentric fragments
was also maximum at 12 h, and later decreased without attaining the normal value,
even up to the last necropsy interval. The percentage of such aberrations was
significantly less in the ASE-pretreated irradiated animals. The incidence of
chromosome breaks and centric rings kept increasing up to d 1, but then declined
gradually and reached zero beginning at d 7; they were significantly lower in the
ASE-treated irradiated group at the early intervals. A significant decrease in
glutathione (GSH) and an increase in lipid peroxidation were observed after
radiation exposure in untreated controls, whereas ASE-pretreated irradiated
animals exhibited a significant increase in GSH and a decrease in lipid
peroxidation; however, the values remained below normal. The results from the
present study suggest that ASE pretreatment provides protection against
radiation-induced chromosomal damage and micronuclei induction in the bone marrow
of mice.


PMID: 20932245 [PubMed - indexed for MEDLINE]


34. Indian J Exp Biol. 2010 Jul;48(7):762-8.

Sub-chronic arsenic exposure aggravates nephrotoxicity in experimental diabetic
rats.

Patel HV, Kalia K.

Laboratory of Biochemistry, BRD School of Biosciences, Sardar Patel University, V
V Nagar 388 120, India.

The present experiment was planned to study nephrotoxicity in experimental
diabetic rats under sub-chronic exposure to arsenic. Alloxan induced diabetic and
control rats were exposed to sodium arsenite (0 and 5.5 mg/kg, orally) for 30
days. More pronounced nephrotoxic effects were noted in arsenic exposed diabetic
group as evidenced by increased blood urea nitrogen, serum creatinine and
relative kidney weight and decreased level of reduced glutathione and glutathione
peroxidase activity compared to non arsenic exposed diabetic group. Increased
level of lipid peroxidation, protein oxidation, superoxide dismutase and catalase
activities under diabetic condition remained unchanged in arsenic exposed
diabetic group compared to unexposed diabetic group.


PMID: 20929060 [PubMed - indexed for MEDLINE]


35. Indian J Exp Biol. 2010 Jul;48(7):752-61.

Prophylactic efficacy of combination of DRDE-07 and its analogues with amifostine
against sulphur mustard induced systemic toxicity.

Gautam A, Gupta A, Lomash V, Pant SC, Vijayaraghavan R.

Defence Research and Development Establishment, Gwalior 474 002, India.
anshoo_gautam@hotmail.com

Sulphur mustard, [bis (2-chloroethyl)] sulphide (SM), is a bifunctional
alkylating agent. SM forms sulphonium ion in the body which alkylates DNA and
several other macromolecules, and induces oxidative stress. Although several
antidotes have been screened for the treatment of systemic toxicity of SM in
experimental animals none of them are recommended so far. In the search for more
effective and less toxic antidotes, various combinations were tried against SM
induced toxicity and skin lesions. SM exposed through percutaneous route was used
to evaluate the prophylactic efficacy of various combinations. Low dose of
DRDE-07 (S-2(2-aminoethylamino) ethyl phenyl sulphide), DRDE-30 [S-2(2-aminoethyl
amino) ethyl propyl sulphide], DRDE-35 [S-2(2-aminoethyl amino) ethyl butyl
sulphide] with amifostine combinations, were given orally 30 min prior to SM
exposure. Significant depletion was observed in body weight, organ body weight
index and hepatic GSH and GSSG content in mice after SM exposure. Pretreatment
with low dose of different combinations of DRDE-07, DRDE-30 and DRDE-35 with
amifostine could recover biochemical alterations and histopathological changes
caused by SM exposures.


PMID: 20929059 [PubMed - indexed for MEDLINE]


36. Appl Microbiol Biotechnol. 2010 Oct 7. [Epub ahead of print]

Functional characterization of a new holin-like antibacterial protein coding gene
tmp1 from goat skin surface metagenome.

Rajesh T, Anthony T, Saranya S, Pushpam PL, Gunasekaran P.

Department of Genetics, Centre for Excellence in Genomic Sciences, School of
Biological Sciences, Madurai Kamaraj University, Madurai, 625 021, India.

We have identified a holin-like gene from a goat skin surface metagenome. The ORF
designated tmp1 coding for 34 amino acids shared sequence similarity with
putative holin-like toxin genes. To analyze the antibacterial activity of tmp1
encoded protein, this ORF was cloned and expressed in Escherichia coli BL21(DE3).
The expressed gene product Tmp1 exhibited antibacterial activity against
Gram-positive bacteria but not to Gram-negative bacteria. A single transmembrane
domain (TMD) was identified within Tmp1 and deletion analysis of the N-terminal
region and TMD indicated TMD to be responsible for antibacterial activity. The
TMD-dependent antibacterial activity was validated using a synthetic peptide with
the amino acid sequence of TMD. Besides antibacterial activity, Tmp1 also
complemented the function of holin in a lysis-defective bacteriophage lambda. To
broaden the spectrum of antibacterial activity, a mutant library of tmp1 was
generated by random mutagenesis. Four mutants with amino acid substitutions at
the N-terminus of Tmp1 exhibited increased antibacterial activity against
Gram-positive and Gram-negative bacteria and were not hemolytic. An improved
activity of these mutant proteins is attributed to their increased
hydrophobicity.


PMID: 20927512 [PubMed - as supplied by publisher]


37. PLoS One. 2010 Sep 30;5(9). pii: e13122.

Studies on a novel serine protease of a ΔhapAΔprtV Vibrio cholerae O1 strain and
its role in hemorrhagic response in the rabbit ileal loop model.

Syngkon A, Elluri S, Koley H, Rompikuntal PK, Saha DR, Chakrabarti MK, Bhadra RK,
Wai SN, Pal A.

Divisions of Pathophysiology, National Institute of Cholera and Enteric Diseases,
Kolkata, West Bengal, India.

BACKGROUND: Two well-characterized proteases secreted by Vibrio cholerae O1
strains are hemagglutinin protease (HAP) and V. cholerae protease (PrtV). The
hapA and prtV knock out mutant, V. cholerae O1 strain CHA6.8ΔprtV, still retains
residual protease activity. We initiated this study to characterize the protease
present in CHA6.8ΔprtV strain and study its role in pathogenesis in rabbit ileal
loop model (RIL). METHODOLOGY/PRINCIPAL FINDINGS: We partially purified the
residual protease secreted by strain CHA6.8ΔprtV from culture supernatant by
anion-exchange chromatography. The major protein band in native PAGE was
identified by MS peptide mapping and sequence analysis showed homology with a
59-kDa trypsin-like serine protease encoded by VC1649. The protease activity was
partially inhibited by 25 mM PMSF and 10 mM EDTA and completely inhibited by EDTA
and PMSF together. RIL assay with culture supernatants of strains C6709 (FA ratio
1.1+/-0.3 n = 3), CHA6.8 (FA ratio 1.08+/-0.2 n = 3), CHA6.8ΔprtV (FA ratio
1.02+/-0.2 n = 3) and partially purified serine protease from CHA6.8ΔprtV (FA
ratio 1.2+/-0.3 n = 3) induced fluid accumulation and histopathological studies
on rabbit ileum showed destruction of the villus structure with hemorrhage in all
layers of the mucosa. RIL assay with culture supernatant of CHA6.8ΔprtVΔVC1649
strain (FA ratio 0.11+/-0.005 n = 3) and with protease incubated with PMSF and
EDTA (FA ratio 0.3+/-0.05 n = 3) induced a significantly reduced FA ratio with
almost complete normal villus structure. CONCLUSION: Our results show the
presence of a novel 59-kDa serine protease in a ΔhapAΔprtV V. cholerae O1 strain
and its role in hemorrhagic response in RIL model.


PMCID: PMC2948034
PMID: 20927349 [PubMed - in process]


38. Natl Med J India. 2010 Mar-Apr;23(2):77-81.

Circulating angiogenic factors in pregnancies complicated by pre-eclampsia.

Varughese B, Bhatla N, Kumar R, Dwivedi SN, Dhingra R.

Department of Anatomy, All India Institute of Medical Sciences, New Delhi 110029,
India.

BACKGROUND: Pre-eclampsia is an inflammatory disorder characterized by diffuse
endothelial dysfunction possibly secondary to impaired trophoblast invasion of
the spiral arteries during implantation. It is associated with alterations in
maternal serum concentrations of vascular endothelial growth factor (VEGF),
placental growth factor (PIGF) and soluble fms-like tyrosine kinase-1 (sFlt-1).
We did a case-control study to ascertain whether pre-eclampsia is associated with
changes in serum concentrations of VEGF, PIGF and sFlt-1 in Indian patients.
METHODS: Serum samples were obtained from 40 women with pre-eclampsia and 40
normotensive, non-proteinuric pregnant women. The levels of VEGF, PIGF and sFlt-1
were analysed using ELISA. RESULTS: In the sera of pregnant women with
pre-eclampsia, the levels of sFlt-1 were significantly higher than those in the
sera of normotensive, non-proteinuric pregnantwomen (median 11295.25 v. 2936.2
pg/ml, p < 0.0001), whereas there was a significant reduction in the levels of
free VEGF (mean [SD] 170.53 [36.56] pg/ml v. 254.61 [47.39] pg/ml, p < 0.0001)
and PIGF (mean [SD] 236.77 [93.70] pg/ml v. 744.98 [168.55] pg/ml, p < 0.0001).
CONCLUSION: An increase in sFlt-1 levels and a simultaneous decrease in free VEGF
and PIGF levels in the sera of women with pre-eclampsia as compared with
normotensive, nonproteinuric pregnant women suggest that an imbalance between the
levels of these pro- and anti-angiogenic factors'may have a role to play in the
pathogenesis of pre-eclampsia.


PMID: 20925202 [PubMed - indexed for MEDLINE]


39. J Phys Chem B. 2010 Nov 11;114(44):14048-58.

Exploring the Changes in the Structure of α-Helical Peptides Adsorbed onto a
Single Walled Carbon Nanotube Using Classical Molecular Dynamics Simulation.

Balamurugan K, Gopalakrishnan R, Raman SS, Subramanian V.

Chemical Laboratory, Central Leather Research Institute, Council of Scientific
and Industrial Research, Adyar, Chennai- 600020, India.

Classical molecular dynamics (MD) simulation has been carried out in an explicit
solvent environment to understand the interaction between the single walled
carbon nanotube (SWCNT) and α-helix. A polyalanine peptide consisting of 40
alanine residues has been chosen as the model for the α-helix (PA(40)). Results
reveal that the SWCNT induces conformational changes in PA(40). Furthermore,
breakage of hydrogen bonds in the chosen model peptides has been observed, which
leads to conformational transitions (α → turns) in different parts of the PA(40).
Owing to these transitions, regions of different structural and energetic
stability are generated in PA(40) which enable the PA(40) to curl around the
surface of the SWCNT. The overall observations obtained from the MD simulations
are not significantly influenced by the starting geometry and the choice of the
force field. Although the qualities of structural information obtained from the
MD simulation using ff03 and OPLS are different, the overall observation derived
from the ff03 is similar to that of OPLS. Results from the MD simulation on the
interaction of the α-helical fragment of the SNARES protein with the SWCNT elicit
that the amino acid composition influences the interaction pattern. The wrapping
of the α-helical fragment of the SNARES onto the SWCNT is similar to that of
PA(40). Overall, there is a considerable decrease in the helical content of
peptides upon interaction with SWCNTs, in agreement with the experimental
findings.


PMID: 20923226 [PubMed - in process]


40. Chem Asian J. 2010 Oct 4. [Epub ahead of print]

The Design of α/β-Peptides: Study on Three-Residue Turn Motifs and the Influence
of Achiral Glycine on Helix and Turn.

Sharma GV, Chandramouli N, Basha SJ, Nagendar P, Ramakrishna KV, Sarma AV.

Organic Chemistry Division III, Indian Institute of Chemical Technology,
Hyderabad 500 607 (India), Fax: (+91) 40-27160387/27193108.

Novel three-residue helix-turn secondary structures, nucleated by a helix at the
N terminus, were generated in peptides that have 'β-Caa-L-Ala-L-Ala,'
'β-Caa-L-Ala-γ-Caa,' and 'β-Caa-L-Ala-δ-Caa' (in which β-Caa is C-linked
carbo-β-amino acid, γ-Caa is C-linked carbo-γ-amino acid, and δ-Caa is C-linked
carbo-δ-amino acid) at the C terminus. These turn structures are stabilized by
12-, 14-, and 15-membered (mr) hydrogen bonding between NH(i)/CO(i+2) (i+2 is the
last residue in the peptide) along with a 7-mr hydrogen bond between
CO(i)/NH(i+2). In addition, a series of α/β-peptides were designed and
synthesized with alternating glycine (Gly) and (S)-β-Caa to study the influence
of an achiral α-residue on the helix and helix-turn structures. In contrast to
previous results, the three 'β-α-β' residues at the C terminus (α-residue being
Gly) are stabilized by only a 13-mr forward hydrogen bond, which resembles an
α-turn. Extensive NMR spectroscopic and molecular dynamics (MD) studies were
performed to support these observations. The influence of chirality and side
chain is also discussed.


PMID: 20922750 [PubMed - as supplied by publisher]