Abstract：
:While hemoglobin is one of the most well characterized proteins due to its function in oxygen transport, few additional properties of hemoglobin have been described. While screening serum samples for novel antimicrobial factors, it was found that intact hemoglobin tetramers, including that from human, exhibited considerable activity against gram-positive and gram-negative bacteria, and fungi. To further characterize this surprising activity, the antimicrobial potency of sections of human hemoglobin was tested against a panel of microorganisms. In all cases separate testing of the alpha and beta subunits provided activity at least as potent as the intact tetramer. This activity is derived from the protein portion of hemoglobin since removal of the heme prosthetic group did not lead to decreases in potency. In addition, cyanogen bromide cleavage of both subunits provided fragments that still contained substantial antimicrobial activity. It has been possible to map specific regions of the human hemoglobin molecule that are responsible for significant antimicrobial activity. The carboxyl terminal thirty amino acids of the beta subunit, which form a cationic alpha-helix based on the crystal structure of the intact tetramer, were active against Escherichia coli, Staphylococcus aureus and Candida albicans. In view of the fact that different hemoglobin-derived peptide fragments exhibit diverse antibiotic activities, it is conceivable that, in addition to its role in oxygen transport. hemoglobin functions as an important multi-defense agent against a wide range of microorganisms.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Parish CA,Jiang H,Tokiwa Y,Berova N,Nakanishi K,McCabe D,Zuckerman W,Xia MM,Gabay JEdoi
10.1016/s0968-0896(00)00263-7subject
Has Abstractpub_date
2001-02-01 00:00:00pages
377-82issue
2eissn
0968-0896issn
1464-3391pii
S0968089600002637journal_volume
9pub_type
杂志文章abstract：:A series of 5-chloro-N-aryl-1H-indole-2-carboxamide derivatives were prepared and evaluated as inhibitors of human liver glycogen phosphorylase a (hLGPa). One compound, 5-chloro-N-[4-(1,2-dihydroxyethyl)phenyl]-1H-indole-2-carboxamide (2f), inhibited hLGPa with an IC(50) of 0.90microM. The pyridine analogue of 2f show...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2008.04.010
更新日期：2008-05-15 00:00:00
abstract：:The efficient synthesis of a new series of polyhydroxylated dibenzyl ω-(1H-1,2,3-triazol-1-yl)alkylphosphonates as acyclic nucleotide analogues is described starting from dibenzyl ω-azido(polyhydroxy)alkylphosphonates and selected alkynes under microwave irradiation. Selected O,O-dibenzylphosphonate acyclonucleotides ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2014.05.020
更新日期：2014-07-15 00:00:00
abstract：:CNS diseases such as Parkinson, schizophrenia, and attention deficit hyperactivity disorder (ADHD) are characterized by a significant alteration of dopamine transporter (DAT) density. Thus, the development of compounds that are able to selectively interact with DAT is of great interest. Herein we describe the design a...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2006.04.019
更新日期：2006-08-01 00:00:00
abstract：:Valinol is part of numerous pharmaceuticals and has various other important applications. Optically pure valinol (ee >99%) was prepared employing different ω-transaminases from the corresponding prochiral hydroxy ketone. By the choice of the enzyme the (R)- as well as the (S)-enantiomer were accessible. Reductive amin...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2014.05.055
更新日期：2014-10-15 00:00:00
abstract：:Leukemia stem cells (LSCs) account for the development of drug resistance and increased recurrence rate in acute myeloid leukemia (AML) patients. Targeted drug delivery to leukemia stem cells remains a major challenge in AML chemotherapy. Overexpressed interleukin-3 receptor alpha chain, CD123, on the surface of leuke...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2016.09.043
更新日期：2016-11-15 00:00:00
abstract：:The need for novel therapeutic options to fight herpesvirus infections still persists. Herein we report the design, synthesis and antiviral evaluation of a new family of non-nucleoside antivirals, derived from 1-[ω-(4-bromophenoxy)alkyl]uracil derivatives--previously reported inhibitors of human cytomegalovirus (HCMV)...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2015.09.033
更新日期：2015-11-01 00:00:00
abstract：:Twenty-eight tetraketones (1-28) with variable substituents at C-7 were synthesized and evaluated as tyrosinase inhibitors. Remarkably compounds 25 (IC(50)=2.06 microM), 11 (IC(50)=2.09 microM), 15 (IC(50)=2.61 microM), and 27 (IC(50)=3.19 microM) were found to be the most active compounds of the series, even better t...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2005.08.029
更新日期：2006-01-15 00:00:00
abstract：:A new meso-2,4,6-trimethoxyphenyl porphyrin covalently linked to a 2',6'-dinitro-4'-trifluoromethylphenyl group by an amine bond 5 and its metal complex with Cd(II) 6 was prepared. The photodynamic activities of 5 and 6 were evaluated in vitro on Hep-2 cells. A considerable increase in the photocytotoxic effect was fo...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(01)00138-9
更新日期：2001-08-01 00:00:00
abstract：:Naltrexone (1), which is a member of the group of competitive opioid antagonists, shows a strong affinity for mu-receptors and its derivatives have been notable as novel receptor antagonists. In this paper, the preparation of several naltrexone derivatives is described; these were used to investigate the role of the o...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2003.10.039
更新日期：2004-01-15 00:00:00
abstract：:Three series of cyclic ketone inhibitors were synthesized and evaluated against the serine protease plasmin. Peptide inhibitors that incorporated 3-oxotetrahydrofuran and 3-oxotetrahydrothiophene 1,1-dioxide groups had the highest activities. Alkylamino substituents, which were designed to bind in the S1 subsite of pl...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2006.08.040
更新日期：2006-12-15 00:00:00
abstract：:Topological evidences for modelling lipophilicity of a large series of diversed compounds have been provided on the basis of distance-based topological indices. A pool of topological indices along with indicator parameters related to the type of the compounds present in the set of 140 compounds were used for this purp...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(02)00299-7
更新日期：2002-12-01 00:00:00
abstract：:Petrosaspongiolides M-R (PM-PR, 1-5) are marine sesterterpenes structurally characterised by a gamma-hydroxybutenolide moiety. They have shown an in vitro and in vivo potent anti-inflammatory activity, mediated by specific inhibition of secretory phospholipase A(2) (sPLA(2) enzymes). The molecular mechanism underlying...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2003.12.038
更新日期：2004-03-15 00:00:00
abstract：:The investigation of Tylosema esculentum (Morama) husks, cotyledons, and tuber yielded griffonilide 2, compound 1, griffonin 3, gallic acid 4, protocatechuic acid 5, β-sitosterol 6, behenic acid 7, oleic acid 8, sucrose 9, 2-O-ethyl-α-D-glucopyranoside 10, kaempferol 11 and kaempferol-3-O-β-D-glucopyranoside 12. The s...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2011.07.006
更新日期：2011-09-01 00:00:00
abstract：:A structural survey of protein Zn2+ binding geometries was instigated based upon the functional requirement of Ras farnesyltransferase for Zn2+. The Cys-X-X-Cys motif found in Zn(2+)-binding proteins such as aspartate transcarbamylase was used as a template to devise a bidentate-coordination model for Cys-A1-A2-X pept...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(00)82044-1
更新日期：1994-09-01 00:00:00
abstract：:The synthesis of a series of 2,4-disubstituted morpholines is described and their affinities at human dopamine receptors reported. The orally bioavailable 7-azaindole compound 11 has nanomolar affinity at the hD4 receptor with > 1000-fold selectivity over the hD2 receptor. ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(97)00176-4
更新日期：1998-01-01 00:00:00
abstract：:Bowman-Birk inhibitor proteins (BBIs), which are potent inhibitors of chymotrypsin-like proteases, do not inhibit human beta-tryptase despite this protein having a chymotrypsin-like fold. We have reported previously that, in contrast, BBI-derived peptides (whose sequences incorporate the solvent exposed reactive site ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2004.09.015
更新日期：2004-12-01 00:00:00
abstract：:Electronic parameters (molecular electrostatic potential MEP, charge distribution on the nitrogen atoms, dipole moment mu and ionization potential IP) were calculated by semiempirical quantum chemistry methods for 2 sets (X = H and m-CF3, the syn- and anti-rotamers of the latter being considered separately) of the 6-a...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(00)82176-8
更新日期：1994-08-01 00:00:00
abstract：:In vitro studies, using combined spectrophotometry and oximetry together with hplc/ms examination of the products of tyrosinase action demonstrate that hydroquinone is not a primary substrate for the enzyme but is vicariously oxidised by a redox exchange mechanism in the presence of either catechol, L-3,4-dihydroxyphe...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2012.05.041
更新日期：2012-07-15 00:00:00
abstract：:The human telomeric sequence d[AGGG(TTAGGG)(3)] has been found to form different types of G-quadruplex structures. NMR revealed that in Na(+) solution this 22 nucleotide (nt) sequence exhibits an antiparallel structure, whereas crystallographic studies in the presence of K(+) showed a dramatically different parallel s...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2006.04.033
更新日期：2006-08-15 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2008.03.049
更新日期：2008-05-01 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(01)00069-4
更新日期：2001-07-01 00:00:00
abstract：:A novel series of indole and benzimidazole derivatives were synthesized and evaluated for their inhibitory activity of rat prostatic 5alpha-reductase. Among these compounds, 4-¿2-[1-(4,4'-dipropylbenzhydryl)indole-5-carboxamido]phenoxy¿buty ric acid (15) and its benzimidazole analogue 25 showed potent inhibitory activ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(98)80018-7
更新日期：1998-12-01 00:00:00
abstract：:Oligosaccharyltransferase (OST) catalyzes the transfer of a branched oligosaccharide from a dolichylpyrophosphate oligosaccharide (Dol-PP-OS) to the asparagine of a nascent polypeptide chain in vivo and peptide substrates in vitro. Here we report the isolation and purification of Dol-PP-OS from bovine pancreas and thy...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(98)00268-5
更新日期：1999-03-01 00:00:00
abstract：:P2X4 receptor has become an interesting molecular target for treatment and PET imaging of neuroinflammation and associated brain diseases such as Alzheimer's disease. This study reports the first design, synthesis, radiolabeling and biological evaluation of new candidate PET P2X4 receptor radioligands using 5-BDBD, a ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2017.05.031
更新日期：2017-07-15 00:00:00
abstract：:A series of 2-substituted 6-t-butylpyridine and 4-t-butylphenyl C-region analogues of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamides were investigated for hTRPV1 antagonism. The analysis of structure activity relationships indicated that the pyridine derivatives generally exhibited a little better antagonism than ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2017.03.004
更新日期：2017-04-15 00:00:00
abstract：:A set of thirty five molecules of 1,3-diaryl-4,5,6,7-tetrahydro-2H-isoindoles endowed with selective COX-2 inhibitory activity was analyzed using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Besides conventional steric and electrostatic fields, seven addi...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(03)00404-8
更新日期：2003-09-01 00:00:00
abstract：:FIKKs are parasite-specific protein kinases with distinctive sequence motifs and their biological roles have not been completely elucidated. Here, we report the first potent Cryptosporidium FIKK (CpFIKK) inhibitor. We identified 4b as a potent (IC50=0.2nM) inhibitor of CpFIKK catalytic activity. In addition, we identi...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2017.01.036
更新日期：2017-03-01 00:00:00
abstract：:D3 receptor radioligands (E)-4,3,2-[11C]methoxy-N-4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl-cinnamoylamides (4-[11C]MMC, [11C]1a; 3-[11C]MMC, [11C]1b; and 2-[11C]MMC, [11C]1c) were synthesized for evaluation as novel potential positron emission tomography (PET) imaging agents for brain D3 receptors. The new tracers 4...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2005.06.055
更新日期：2005-11-15 00:00:00
abstract：:Glucose flux through glucokinase (GK) controls insulin release from the pancreas in response to high levels of glucose. Flux through GK is also responsible for reducing hepatic glucose output. Since many individuals with type 2 diabetes appear to have an inadequacy or defect in one or both of these processes, identify...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2019.115232
更新日期：2020-01-01 00:00:00
abstract：:Large series of O-alkyl derivatives (methyl and benzyl) of silybin and 2,3-dehydrosilybin was prepared. Selective alkylation of the silybin molecule was systematically investigated. For the first time we present here, for example, preparation of 19-nor-2,3-dehydrosilybin. All prepared silybin/2,3-dehydrosilybin deriva...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2006.01.035
更新日期：2006-06-01 00:00:00
