- Inhibition of urease enzyme activity by urea and thiourea derivatives of dipeptides conjugated 2, 3-dichlorophenyl piperazine
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Objective: Studies on enzyme inhibition remain an important area of pharmaceutical research since these studies have led to the discoveries of drugs used in a variety of physiological conditions. In search of novel urease enzyme inhibitors, four dipeptide
- Suyoga Vardhan,Kumara,Pavan Kumar,Channe Gowda
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- Structure-activity analysis of peptidic Chlamydia HtrA inhibitors
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Chlamydia trachomatis high temperature requirement A (CtHtrA) is a serine protease that performs proteolytic and chaperone functions in pathogenic Chlamydiae; and is seen as a prospective drug target. This study details the strategies employed in optimizi
- Agbowuro, Ayodeji A.,Hwang, Jimin,Peel, Emma,Mazraani, Rami,Springwald, Alexandra,Marsh, James W.,McCaughey, Laura,Gamble, Allan B.,Huston, Wilhelmina M.,Tyndall, Joel D.A.
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p. 4185 - 4199
(2019/08/07)
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- Stereochemical basis for the anti-chlamydial activity of the phosphonate protease inhibitor JO146
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JO146, a mixture of two diastereomers of a peptidic phosphonate inhibitor for Chlamydial HtrA (CtHtrA), has reported activity against Chlamydia species in both human and koala. In this study we isolated the individual diastereomers JO146-D1 and JO146-D2 (
- Agbowuro, Ayodeji A.,Mazraani, Rami,McCaughey, Laura C.,Huston, Wilhelmina M.,Gamble, Allan B.,Tyndall, Joel D.A.
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p. 1184 - 1190
(2017/10/25)
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- Synthesis, characterization and in vitro DNA binding and cleavage studies of Cu(II)/Zn(II) dipeptide complexes
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Novel dipeptide complexes Cu(II)?Val-Pro (1), Zn(II)?Val-Pro (2), Cu(II)?Ala-Pro (3) and Zn(II)?Ala-Pro (4) were synthesized and thoroughly characterized using different spectroscopic techniques including elemental analyses, IR, NMR, ESI-MS and molar conductance measurements. The solution stability study carried out by UV-vis absorption titration over a broad range of pH proved the stability of the complexes in solution. In vitro DNA binding studies of complexes 1-4 carried out employing absorption, fluorescence, circular dichroism and viscometric studies revealed the binding of complexes to DNA via groove binding. UV-vis titrations of 1-4 with mononucleotides of interest viz., 5′-GMP and 5′-TMP were also carried out. The DNA cleavage activity of the complexes 1 and 2 were ascertained by gel electrophoresis assay which revealed that the complexes are good DNA cleavage agents and the cleavage mechanism involved a hydrolytic pathway. Furthermore, in vitro antitumor activity of complex 1 was screened against human cancer cell lines of different histological origin.
- Arjmand, Farukh,Jamsheera,Mohapatra
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- NOVEL DIPEPTIDYL PEPTIDASE (DP-IV) COMPOUNDS
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The present invention is directed to novel compounds of formula I and pharmaceutically acceptable salts, enantiomers thereof having inhibiting properties of dipeptidyl peptidase IV enzyme (DP-IV inhibitors). The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds along with its composition in the prevention or treatment of diseases associated with DP-IV enzyme. wherein, A is defined as R3-R4 wherein R3 and R4 are together or independently defined as peptides having amino acids ranging from 1 to 10, B is chemical bond between peptide and substituted amine, R1, and R2 are as defined in specification,
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Page/Page column 8
(2010/04/06)
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- Synthesis and antimicrobial activity of 7-Amino cephalosporanic acid derivatives of amino acids and peptides
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A novel series of 7-amino cephalosporanic acid derivatives of amino acid and peptides were synthesized by solution phase technique. The synthesized compounds were tested for their biological activities against bacterial and fungal organisms. All the compounds showed potent antifungal activity and most of the compounds have shown moderate antibacterial activities. The structures of the newly synthesized compounds were confirmed by IR, 1H NMR and mass spectral analysis.
- Himaja,Desai, Siddharth,Sambanthan, A. Thirugnana,Ranjitha
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scheme or table
p. 2914 - 2918
(2010/11/05)
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- Novel C2-C3′ N-peptide linked macrocyclic taxoids. Part 2: Synthesis and biological activities of docetaxel analogues with a peptide side chain at C2 and their macrocyclic derivatives
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The synthesis of a series of novel docetaxel analogues possessing a peptide side chain at the C2 position as well as peptide macrocyclic taxoids is described. These compounds were designed to mimic a region of the α-tubulin loop equivalent to the paclitax
- Larroque, Anne-Laure,Dubois, Joelle,Thoret, Sylviane,Aubert, Genevieve,Chiaroni, Angele,Gueritte, Francoise,Guenard, Daniel
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p. 563 - 574
(2008/03/12)
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- N-bromosuccinimide oxidation of dipeptides and their amino acids: Synthesis, kinetics and mechanistic studies
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Dipeptides (DP), namely valyl-glycine (Val-Gly), alanyl-proline (Ala-Pro), and valyl-proline (Val-Pro) were synthesized by classical solution phase methods and characterized. The kinetics of oxidation of amino acids (AA) and DP by N-bromosuccinimide (NBS) was studied in the presence of perchlorate ions in acidic medium at 28°C. The reaction was followed spectrophotometrically at λmax = 240 nm. The reactions follow identical kinetics, being first order each in [NBS], [AA], and [DP]. No effect on [H+], reduction product [succinimide], and ionic strength was observed. Effects of varying dielectric constant of the medium and addition of anions such as chloride and perchlorate were studied. Activation parameters have been computed. The oxidation products of the reaction were isolated and characterized. The proposed mechanism is consistent with the experimental results. An apparent correlation was noted between the rate of oxidation of AA and DP.
- Linge Gowda,Kumara,Channe Gowda,Rangappa
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p. 376 - 385
(2008/02/08)
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- Structure-based design, synthesis and biochemical testing of novel and potent Smac peptido-mimetics
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Structure-based design, chemical synthesis and biochemical testing of a series of novel Smac peptido-mimetics as inhibitors of XIAP protein are described. The most potent compound, 6j, has a binding affinity (Ki value) of 24 nM to XIAP BIR3 pro
- Sun, Haiying,Nikolovska-Coleska, Zaneta,Chen, Jianyong,Yang, Chao-Yie,Tomita, York,Pan, Hongguang,Yoshioka, Yoshiko,Krajewski, Krzysztof,Roller, Peter P.,Wang, Shaomeng
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p. 793 - 797
(2007/10/03)
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- Inhibitors of tripeptidyl peptidase II. 3. Derivation of butabindide by successive structure optimizations leading to a potential general approach to designing exopeptidase inhibitors
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The cholecystokinin-8 (CCK-8)-inactivating peptidase is a serine peptidase that has been shown to be a membrane-bound isoform of tripeptidyl peptidase II (EC 3.4.14.10). It cleaves the neurotransmitter CCK-8 sulfate at the Met-Gly bond to give Asp-Tyr(SO
- Ganellin, C. Robin,Bishop, Paul B.,Bambal, Ramesh B.,Chan, Suzanne M. T.,Leblond, Bertrand,Moore, Andrew N. J.,Zhao, Lihua,Bourgeat, Pierre,Rose, Christiane,Vargas, Froylan,Schwartz, Jean-Charles
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p. 7333 - 7342
(2007/10/03)
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- Synthetic studies on cyclic octapeptides: Yunnanin F and Hymenistatin
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Two biologically active cyclic peptides, Yunnanin F 8 and Hymenistatin 16 were synthesized and the structures were established on the basis of analytical, IR, NMR and mass spectral data. The newly synthesized compounds were screened for their antimicrobia
- Poojary, Boja,Belagali, Shiddappa L.
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p. 407 - 412
(2007/10/03)
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- Synthesis of Nα-protected peptide acids by the N→ C chain extension employing O,N-bis-trimethylsilyl-amino acids using the mixed anhydride method
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Synthesis of Nα-protected peptide acids employing N→C extension strategy using in situ generated X-NH-CHR′-CO-O-CO- iBu and O,N-bis-trimethylsilyl-amino acids has been accomplished. The coupling is very rapid and efficient. The yield
- Tantry, Subramanyam J.,Babu, Vommina V. Suresh
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p. 1282 - 1287
(2007/10/03)
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- Synthesis of a novel cis-proline-derived cyclic type VI β-turn mimic via ring-closing metathesis
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A cis-proline derived cyclic mimic of a type VI β-turn is synthesized via a ring-closing metathesis reaction. The solution NMR conformational study indicates that the major conformer of the cyclic peptide adopts a type VIa β-turn in CDCl3 and a type VIb β-turn in DMSO-d6.
- Boruah, Anima,Rao, I. Nageshwar,Nandy, Jyoti Prokash,Kumar, S. Kiran,Kunwar,Iqbal, Javed
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p. 5006 - 5008
(2007/10/03)
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- Inhibitors of tripeptidyl peptidase II. 2. Generation of the first novel lead inhibitor of cholecystokinin-8-inactivating peptidase: A strategy for the design of peptidase inhibitors
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The cholecystokinin-8 (CCK-8)-inactivating peptidase is a serine peptidase which has been shown to be a membrane-bound isoform of tripeptidyl peptidase II (EC 3.4.14.10). It cleaves the neurotransmitter CCK-8 sulfate at the Met-Gly bond to give Asp-Tyr(SO3H)-Met-OH + Gly-Trp-Met-Asp-Phe-NH2. In seeking a reversible inhibitor of this peptidase, the enzymatic binding subsites were characterized using a fluorimetric assay based on the hydrolysis of the artificial substrate Ala-Ala-Phe-amidomethylcoumarin. A series of di- and tripeptides having various alkyl or aryl side chains was studied to determine the accessible volume for binding and to probe the potential for hydrophobic interactions. From this initial study the tripeptides Ile-Pro-Ile-OH (K(i) = 1 μM) and Ala-Pro-Ala-OH (K(i) = 3 μM) and dipeptide amide Val-Nvl-NHBu (K(i) = 3 μM) emerged as leads. Comparison of these structures led to the synthesis of Val-Pro-NHBu (K(i) = 0.57 μM) which served for later optimization in the design of butabindide, a potent reversible competitive and selective inhibitor of the CCK-8-inactivating peptidase. The strategy for this work is explicitly described since it illustrates a possible general approach for peptidase inhibitor design.
- Ganellin, C. Robin,Bishop, Paul B.,Bambal, Ramesh B.,Chan, Suzanne M. T.,Law, James K.,Marabout, Benoit,Luthra, Pratibha Mehta,Moore, Andrew N. J.,Peschard, Olivier,Bourgeat, Pierre,Rose, Christiane,Vargas, Froylan,Schwartz, Jean-Charles
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p. 664 - 674
(2007/10/03)
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- (Nitro) hymenamide A, unusual biologically active cyclic peptide
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A new biological active cyclic peptide (Nitro) Hymenamide A has been synthesized and the structure was established on the basis of analytical, IR, NMR and mass spectral data. The new compound was subjected to both antimicrobial and pharmacological studies.
- Belagali,Himaja,Kumar,Thomas,Prakasini,Poojary
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p. 160 - 164
(2007/10/03)
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- Inhibition of human leukocyte elastase (HLE) by N-substituted peptidyl trifluoromethyl ketones
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A series of tripeptides possessing trifluoromethyl or aryl ketone residues at P1 were prepared and evaluated both in vitro and in vivo as potential inhibitors of human leukocyte elastase (HLE). Tripeptides containing non naturally occurring N-substituted glycine residues at the P2-position have been demonstrated to be potent in vitro inhibitors of HLE, with IC50 values in the submicromolar range. Sterically demanding substituents on the P2- nitrogen have no detrimental effect on in vitro potency. The inhibition process presumably acts via hemiketal formation with the active site Ser195 of HLE, and is facilitated by the strongly electron withdrawing trifluoromethyl functionality. Deletion of the amino acid at the P3-subsite region affords inactive compounds. Valine is the preferred residue at the P1-position, whereas the corresponding glycine, alanine, α,α- dimethylglycine, or phenylalanine analogues are all inactive. The compounds described herein all confer a high degree of in vitro specificity when tested against representative cysteine, aspartyl, metallo, and other serine proteases. One of the most potent in vitro inhibitors is (3RS)-N-[4[[[(4- chlorophenyl)sulfonyl]amino]carbonyl]phenyl]oxomethyl]-L-valyl-N-(2,3- dihydro-1H-inden-2-yl)glycine N-[3-(1,1,1-trifluoro-4-methyl-2- oxopentyl)amide (20i; BI-RA-260) (IC50 = 0.084 μM). Compound 20i was also tested in hamsters in an elastase-induced pulmonary hemorrhage (EPH) model. In this model, intratracheal (it.) administration of 20i, 5 min prior to HLE challenge, effectively inhibited hemorrhage in a dose-dependent manner with an ED50 of 4.8 μg. The inhibitor 20i, 20 μg administered it. 24, 48, and 72 h prior to HLE challenge, exhibits significant inhibition against hemorrhage at all time points (97%, 64% and 49%, respectively). In a 21-day chronic model of emphysema in hamsters, 200 μg of HLE administered it. caused an elastase-induced emphysema in the lungs which can be quantitated histologically utilizing image analysis. In this assay, 20i significantly inhibited pulmonary lesions associated with septal destruction and increased alveolar spaces, when dosed at 20 μg it. 5 min prior to challenge with HLE.
- Skiles,Fuchs,Miao,Sorcek,Grozinger,Mauldin,Vitous,Mui,Jacober,Chow,Matteo,Skoog,Weldon,Possanza,Keirns,Letts,Rosenthal
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p. 641 - 662
(2007/10/02)
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- SYNTHESIS AND IMMUNOREGULATORY PROPERTIES OF FRAGMENTS OF A PROLINE-RICH POLYPEPTIDE FROM OVINE COLOSTRUM
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Proline-rich-polypeptide (PRP) isolated from ovine colostrum produces a regulatory effect on the immune response.A nonapeptide fragment of PRP obtained by chymotryptic digestion (Val-Glu-Ser-Tyr-Val-Pro-Leu-Phe-Pro) shows biological activity similar to PR
- Kubik, Aleksandra,Szewczuk, Zbigniew,Siemion, Ignacy Z.,Janusz, Maria,Wieczorek, Zbigniew,et al.
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p. 457 - 464
(2007/10/02)
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- PROLINE DERIVATIVES
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Proline derivatives of the formulae: STR1 wherein R 1 through R 11 have defined values, and acid-and base-addition salts thereof, and equilibrium addition compounds of the aldehyde group thereof; processes for their preparation; pharmaceutical compositions; and intermediates for preparing said proline derivatives. The proline derivatives are human leukocyte elastase inhibitors which are useful, for example, in treating pulmonary emphysema.
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- Synthesis of porcine motilin via its sulfoxides
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The protected segments corresponding to sequences 1-8 and 9-22 proposed for porcine motilin were synthesized mainly by the repetitive excess mixed anhydride (REMA) method.Mixed anhydride coupling of the segments gave protected motilin sulfoxide (Scheme).D
- Izeboud, E.,Beyerman, H. C.
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p. 124 - 130
(2007/10/02)
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