共查询到20条相似文献,搜索用时 31 毫秒
1.
Zoltan Dekan Filip A. Paczkowski Richard J. Lewis Paul F. Alewood 《International journal of peptide research and therapeutics》2007,13(1-2):307-312
The 13-residue peptide, χ-conotoxin MrIA extracted from the venom of Conus marmoreus, is a potent and selective inhibitor of the human noradrenaline transporter (NET). With the aim of improving its biophysical
properties, chemical modifications were performed including the attachment of a lipophilic amino acid at the N-terminus and
cyclisation of the peptide backbone with functionality introduced into the linker. All χ-conotoxin MrIA analogues were assembled
on solid phase by highly optimised Boc chemistry and N- to C-cyclic analogues accessed by cysteine-mediated intramolecular
native chemical ligation. In vitro biological activity at the human NET was evaluated by functional assays. All analogues inhibited the uptake of [3H]noradrenaline with comparable potencies to that of the native peptide, with one of the analogues, the linear N-terminal
aminotetradecanoyl MrIA showing a 3-fold increase in potency (p < 0.05). 相似文献
2.
K. M. Sivanandaiah S. Gurusiddappa D. Channe Gowda V. V. Suresh Babu 《Journal of biosciences》1989,14(3):311-317
Using mainly 9-fluorenylmethyloxycarbonyl amino acid 2, 4, 5-trichlorophenyl esters in the presence of 1-hydroxybenzotriazole
and the solid supportp-alkoxybenzyl alcohol resin, synthesis of luteinizing hormone releasing hormone analogues was carried out with minimal side-chain
protection. Catalytic transfer hydrogenation was employed for removal of NO2 and Z-groups from Arg and < Glu respectively avoiding the use of HF and this led to good yields. An aromatic, hydrophilic
amino acid, D-(p-hydroxyphenyl) glycine was incorporated into luteinizing hormone releasing hormone molecule along with other modifications.
The agonistic as well as antagonistic activities of all the peptides have been studied 相似文献
3.
Jean-Alain Fehrentz Corine Genu-Dellac Muriel Amblard Franclois Winternitz Albert Loffet Jean Martinez 《Journal of peptide science》1995,1(2):124-131
N-Urethane-protected N-carboxyanhydrides (UNCAs) are very reactives. They have been successfully used in peptide synthesis, in both solution and solid phase. We have demonstrated that UNCAs are interesting starting materials for the synthesis of various amino acid derivatives. Chemoselective reduction of UNCAs with sodium borohydride led the corresponding N-protected β amino alcohols. Reaction of UNCAs with Meldrum's acid, followed by cyclisation, yielded enantiomerially pure tetramic acid derivatives. Diastereoselective reduction of tetramic acid derivatives produced (4S,5S)-N-alkoxycarbonyl-4-hydroxy-5-alkylpyrrolidin-2-ones derived from amino acids, which after hydrolysis yielded statine and statine analogues. Tetramic acid derivatives could also be obtained by reaction of UNCAs with benzyl ethyl followed by hydrogenolytic deprotection and decarboxylation. UNCAs also reacted with phosphoranes to produce the ketophosphorane in excellent yields. Subsequent oxidation with oxone or with [bis(acetoxy)-iodol]-benzene produced vicinal tricarbonyl derivatives. These reactions usually proceeded smoothly and with high yields. 相似文献
4.
The opioid pentapeptide leucine-enkephalinamide and eleven of its analogues have been synthesised by the solid phase technique
employing mostly 9-fluoroenylmethyloxycarbonyl amino acid active esters in the presence of 1-hydroxybenzotriazole. Both the
conventional chloromethylated copolystyrene-2% divinylbenzene resin as well asp-alkoxybenzyl alcohol resin were employed and it was observed that yields were uniformly better with the latter resin. The
analogues were made by affecting single or multiple replacements of amino acids involving positions 1,2 and 5. Some of the
analogues were found to be more potent than morphine in the guinea pig ileum assay. 相似文献
5.
Synthesis and Structure-activity Relationships of Amastatin Analogues,Inhibitors of Aminopeptidase A
Hiroyasu Tobe Hajime Morishima Takaaki Aoyagi Hamao Umezawa Kunio Ishiki Kenji Nakamura 《Bioscience, biotechnology, and biochemistry》2013,77(7):1865-1872
Stereoisomers and analogues of amastatin, [(2S,3R)-3-amino-2-hydroxy-5-methylhexanoyl]-l-Val-l-Val-l-Asp, were synthesized and their inhibitory activities towards aminopeptidase A (AP-A) and other arylamidases tested. Among the four stereoisomers of a new amino acid residue in amastatin, the 2S stereoisomers exhibited strong activity. In a series of compounds in which the C-terminal amino acid of amastatin was substituted by other amino acids, the one containing Asp or Glu showed the strongest activity towards AP-A. In a series of compounds in which the second or third residue from the amino terminal of amastatin was substituted by other amino acids, the one containing hydrophobic amino acids showed strong activity. In the study of the relationship of the length of the peptide chain and inhibitory activity, the activity towards AP-A was seen to increase until the length of the peptide reached that of a tetrapeptide. 相似文献
6.
Effects of the precursors and intermediates of the NAD biosynthetic pathway, and of quinolinate analogues etc. on hog liver crystalline quinolinate phosphoribosyltransferase (an intermediary enzyme in the de novo NAD biosynthetic pathway) activity were investigated. The enzyme activity was inhibited by many kinds of nucleotides, phthalic acid and SH reagents. But amino acids, nicotinic acid and nicotinamide had practically no effect. The apparent inhibition by ATP removed by raising Mg2+ concentration. Phthalic acid was proved to be a competitive inhibitor to quinolinic acid. The Ki value for phthalic acid was calculated at 1.7 × 10?4 m by a Dixon plot. 相似文献
7.
Effects of Hydroxyproline and other Amino Acid Analogues on the Growth of Pea Root Segments 总被引:1,自引:0,他引:1
Changes in the lengths and growth rates of isolated 2–4 mm pea root segments, cultured in sucrose media under aseptic conditions, were paralleled by changes in invertase development and in chloride and leucine uptakes. The amino acid analogues o-, m- and p-fluorophenylalanine, azetidine-2-carboxylic acid and ethionine inhibited growth with corresponding changes in invertase activity and in chloride and leucine uptakes. In contrast hydroxyproline, which under the conditions used may be regarded as an analogue of proline, enhanced both the growth rate and duration of growth but had little effect on the several parameters of protein synthesis which were measured. No amino acid tested affected changes in growth, invertase activity or the uptake of chloride and leucine, but they prevented the effects of the corresponding analogues. The results show that although extension growth is dependent on continuous protein synthesis, only specific proteins, probably in the cell wall, play a key role in this process. 相似文献
8.
Protegrin antimicrobial peptides (AMP) possess a high activity against a variety of microorganisms. In the present contribution, we analyse the structural requirements of protegrin analogues reported by Ostberg and Kaznessis (Peptides 2005; 26: 197) for having antimicrobial activity against several microbial species by using interpretable QSAR models. Models were carried out using multiple linear regression (MLR) combined with genetic algorithm (GA) and smoothed amino acid sequence properties were employed for characterizing the peptide dataset. The main advantage of smoothing process is the alteration of local amino acid properties by the properties of the amino acids in the closer neighbourhood. We report models encompassing different characteristics for describing the activities against different microbial species. Our results suggest the existence of specific mechanisms of action for protegrin analogues against different microbial species. 相似文献
9.
A general method for preparation of N‐Boc‐protected or N‐Fmoc‐protected α,β‐didehydropeptide building blocks and their use in the solid‐phase peptide synthesis
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N‐(tert‐butyloxycarbonyl) or N‐(9‐fluorenylmethoxycarbonyl) dipeptides with C‐terminal (Z)‐α,β‐didehydrophenylalanine (?ZPhe), (Z)‐α,β‐didehydrotyrosine (?ZTyr), (Z)‐α,β‐didehydrotryptophan (?ZTrp), (Z)‐α,β‐didehydromethionine (?ZMet), (Z)‐α,β‐didehydroleucine (?ZLeu), and (Z/E)‐α,β‐didehydroisoleucine (?Z/EIle) were synthesised from their saturated analogues via oxidation of intermediate 2,5‐disubstituted‐oxazol‐5‐(4H)‐ones (also known as azlactones) with pyridinium tribromide followed by opening of the produced unsaturated oxazol‐5‐(4H)‐one derivatives in organic‐aqueous solution with a catalytic amount of trifluoroacetic acid or by a basic hydrolysis. In all cases, a very strong preference for Z isomers of α,β‐didehydro‐α‐amino acid residues was observed except of the ΔIle, which was obtained as the equimolar mixture of Z and E isomers. Reasons for the (Z)‐stereoselectivity and the increased stability of the aromatic α,β‐didehydro‐α‐amino acid residue oxazol‐5‐(4H)‐ones over the corresponding aliphatic ones are also discussed. It is the first use of such a procedure to synthesise peptides with the C‐terminal unsaturated residues and a peptide with 2 consecutive ΔPhe residues. This approach is very effective especially in the synthesis of peptides with aliphatic α,β‐didehydro‐α‐amino acid residues that are difficult to obtain by other methods. It allowed the first synthesis of the ?Met residue. It is also more cost‐effective and less laborious than other synthesis protocols. The dipeptide building blocks obtained were used in the solid‐phase synthesis of model peptides on a polystyrene‐based solid support. Peptides containing aromatic α,β‐didehydro‐α‐amino acid residues were obtained with PyBOP or TBTU as a coupling agent with good yields and purities. In the case of aliphatic α,β‐didehydro‐α‐amino acid residues, a good efficiency was achieved only with DPPA as a coupling agent. 相似文献
10.
Taran S. A. Esikova T. Z. Mustaeva L. G. Baru M. B. Alakhov Yu. B. 《Russian Journal of Bioorganic Chemistry》2002,28(5):357-362
Three 18-membered analogues of the N-terminal fragment of the sarcotoxin IA cationic antimicrobial peptide were synthesized by the solid phase method of peptide synthesis with the use of swellographic monitoring. The ability of these peptides to inhibit the growth of various bacteria in culture medium and their hemolytic activity in experiments on human erythrocytes were studied. The analogue completely corresponding to the N-terminal amino acid sequence of the natural sarcotoxin IA with the amide group on its C-terminus exhibited higher antibacterial activity. The presence of carboxyl group on the C-terminus or the substitution of Tyr for Trp2 resulted in a decrease in the antimicrobial activity of the peptide. Our results indicate that the amphiphilic N-terminal peptide corresponding to the 1–18 sequence of sarcotoxin IA involves the moieties responsible for the antimicrobial activity of the antibiotic. 相似文献
11.
The susceptibility ofBacillus subtilis to amino acid analogues was found to be markedly influenced by the carbon source used in the test media. Thialysine inhibited
the bacterium with a greater number of carbon sources than the other two analogues tested. 5-Hydroxylysine was inhibitory
with glycerol, lactose,D-xylose,L-arabinose and soluble starch while ethionine showed toxicity with lactose,D-xylose andL-arabinose. None of these analogues were toxic at the levels tested whenD-galactose was used as carbon source. The bacterium was not susceptible to thialysine with glycerol, to 5-hydroxylysine withL-arabinose and to ethionine with lactose. 相似文献
12.
《Bioscience, biotechnology, and biochemistry》2013,77(8):2074-2081
Pseudomonas sp. A-01, isolated as a strain with chitosan-degrading activity, produced a 28 kDa chitosanase. Following purification of the chitosanase (Cto1) and determination of its N-terminal amino acid sequence, the corresponding gene (cto1) was cloned by a reverse-genetic technique. The gene encoded a protein, composed of 266 amino acids, including a putative signal sequence (1-28), that showed an amino acid sequence similar to known family-46 chitosanases. Cto1 was successfully overproduced and was secreted by a Brevibacillus choshinensis transformant carrying the cto1 gene on expression plasmid vector pNCMO2. The purified recombinant Cto1 protein was stable at pH 5–8 and showed the best chitosan-hydrolyzing activity at pH 5. Replacement of two acidic amino acid residues, Glu23 and Asp41, which correspond to previously identified active centers in Streptomyces sp. N174 chitosanase, with Gln and Asn respectively caused a defect in the hydrolyzing activity of the enzyme. 相似文献
13.
Dantcho L. Danalev Lyubomir T. Vezenkov Valentin Lozanov Anastasia Bakalova 《International journal of peptide research and therapeutics》2010,16(2):107-110
A series of new low molecular weight peptide inhibitors, antistasin and ghilantens fragment analogues was designed and synthesized by manual solid phase peptide synthesis. These compounds only differ either by the amino acid placed in position 109 (different basic amino acids) and 115 position (Val or Ile) or 116 position Pro (as free acid or as amide). The anticoagulant activity of the different synthesized peptide mimetics was measured. Further the IC50 was obtained by means of Activated Partial Thromboplastin Time measurement. Using Mihaelis–Menthen equation the mixed type of inhibition toward thrombin and Factor Xa is determined. 相似文献
14.
Marina Gobbo Elisabetta Merli Barbara Biondi Simona Oancea Antonio Toffoletti Fernando Formaggio Claudio Toniolo 《Journal of peptide science》2012,18(1):37-44
A set of analogues of the 14‐residue peptaibol tylopeptin B, containing the stable free‐radical 4‐amino‐1‐oxyl‐2,2,6,6,‐tetramethylpiperidine‐4‐carboxylic acid (TOAC) at one or two selected positions, was synthesized by the solid‐phase methodology. A solution conformational analysis performed by FTIR absorption and CD suggests that, in membrane‐mimicking solvents, the labeled tylopeptin B analogues preserve the helical propensity of the parent peptide, with a preference for the α‐helix or the 310‐helix type depending upon the nature of the solvent. In aqueous environment, the spin‐labeled analogues present a higher content of helical conformation as a consequence of the strong helix promoter effect of the conformationally constrained TOAC residue. We observed a progressive increase of the quenching effect of the nitroxyl radical on the fluorescence of the N‐terminal tryptophan as TOAC replaces the Aib residue at positions 13, 8, and 4, respectively. A membrane permeabilization assay performed on two selected analogues, TOAC8‐ and TOAC13‐tylopeptin B, showed that the labeled peptides exhibit membrane‐modifying properties comparable with those of the natural peptaibiotic. We conclude that our TOAC paramagnetic analogues of tylopeptin B are good models for a detailed ESR investigation of the mechanism of membrane permeabilization induced by medium‐length peptaibiotics. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
15.
Kuczer Mariola Rosiński Grzegorz Issberner Jonathan Osborne Richard Konopińska Danuta 《International journal of peptide research and therapeutics》1998,5(5-6):387-389
Summary We have extended our work on structure/activity relationship studies of the neuropeptiden proctolin (H-Arg-Tyr-Leu-Pro-Thr-OH)
by evaluating the effects of the following proctolin analogues: H-X1-Tyr-Leu-Pro-Thr-OH, where X1=d-Arg(I),N-Me-Arg (II), Can (III), Orn(di-Me) (IV), Orn (iPr) (V), Lys(N, N-di-Me) (VI), Lys(iPr) (VII), Lys(Nic) (VIII) andd-Lys(Nic) (IX). In analogues I–IX, the N-terminal Arg residue was replaced by basic amino acid derivatives with peptides containing
amino acid residues with an isosteric system on the back side chain relative to Arg (compounds III, V and VI) orhomo-Arg (compound VII). Analogues I–IX were evaluated for myotropic activity on thein vitro heart preparation ofTenebrio molitor, whereas peptides II, V, and VII–IX were tested for contractile activity on the isolated foregut of locustSchistocerca gregaria. Peptide II and III showed full cardiotropic activity inT. molitor while peptides V and VII showed 40% and 15%, respectively, locust-gut contracting activity of proctolin. 相似文献
16.
Maud Antoine Guillaume Le Baut Michael Czech Silke Baasner Eckhard Gunther 《Journal of enzyme inhibition and medicinal chemistry》2013,28(5):686-695
New series of analogues of N-(pyridin-4-yl)-2-[1-(4-chlorobenzyl)-indol-3-yl]glyoxamide D-24851 were synthesized, characterized and tested for their in vitro anticancer properties. In the first series, an amino acid spacer was introduced in the glyoxamide chain of D-24851. In the second series, the glyoxamide chain was moved to positions 4 and 5 of indole skeleton. These new compounds were tested on four cancer cell lines (KB, SK-OV-3, NCI-H460 and SF-268), with promising activity for the glycine derivative. 相似文献
17.
Charmaine B. Mendoza Dan Jethro M. Masacupan Dessa Camille R. Batoctoy Eizadora T. Yu Arturo O. Lluisma Lilibeth A. Salvador‐Reyes 《Journal of peptide science》2019,25(7)
Two conomarphins were purified as the major component of the venom of Conus eburneus. Conomarphins Eb1 and Eb2 showed biological activity in the mollusk Pomacea padulosa, causing sluggishness and retraction of siphon, foot, and cephalic tentacles. To further probe the effects of conserved amino acids and posttranslational modifications in conomarphins, we prepared four synthetic analogues: conomarphin Eb1 Hyp10Pro, Hyp10Ala, d ‐Phe13Ala, and l ‐Phe13 variants. Structure‐activity relationship analysis indicated that d ‐Phe13 is critical to the biological activity of conomarphins. In contrast, amino acid changes at position 10 and removal of posttranslational modification in Hyp10Pro can be tolerated. The high expression level and observed mollusk activity of conomarphins may suggest their potential role as defensive arsenal of Conoidean snails against other predatory gastropods. 相似文献
18.
François Tillequin 《Phytochemistry Reviews》2007,6(1):65-79
The chemical diversity of alkaloids in the Rutaceae is correlated with biosynthetic pathways involving various aromatic amino
acid precursors, tyrosine, tryptophan, histidine, and anthranilic acid. The interest of rutaceous polyheteroaromatic alkaloids
as models for the development of anticancer agents relies on their frequent ability to interact with DNA or with systems involved
in the control of its topology, repair, and replication. Fagaronine and nitidine, from Zanthoxylum, demonstrate antileukemic activity, associated with topoisomerases inhibition. Evodiamine from Euodia rutaecarpa, displays antimetastatic properties. The pyranoacridone acronycine, from Sarcomelicope, exhibits antitumor activity against a broad spectrum of solid tumors. Development of synthetic analogues based on this latter
natural product template followed the isolation of the unstable acronycine epoxide, which led to a hypothesis of bioactivation
of acronycine by transformation of the 1,2-double bond into the corresponding oxirane. 1,2-Diacyloxy-1,2-dihydroacronycine
derivatives exhibited antitumor properties, with a broadened spectrum of activity and an increased potency. The demonstration
that acronycine interacted with DNA led to develop benzo[a], [b], and [c]acronycine analogs. Benzo[a] and [b] derivatives displayed significant antitumor activities. 1,2-Dihydroxy-1,2-dihydrobenzo[b]acronycine esters and diesters were active in human orthotopic models of cancers xenografted in nude mice. The activity of
these compounds was correlated with their ability to give covalent adducts with DNA, involving reaction between the N-2 amino
group of guanines and the ester group at the benzylic position of the drug. Cis-1,2-diacetoxy-1,2-dihydrobenzo[b]acronycine, currently developed under the code S23906-1, successfully underwent phase I and is currently under phase II clinical
trials. 相似文献
19.
Lim WJ Hong SY An CL Cho KM Choi BR Kim YK An JM Kang JM Lee SM Cho SJ Kim H Yun HD 《Applied microbiology and biotechnology》2005,68(1):46-52
Pectobacterium chrysanthemi PY35 secretes the endoglucanase Cel5Z, an enzyme of the glycoside hydrolase family 5. Cel5Z is a 426 amino acid, signal peptide (SP)-containing protein composed of two domains: a large N-terminal catalytic domain (CD; 291 amino acids) and a small C-terminal cellulose binding domain (CBD; 62 amino acids). These two domains are separated by a 30 amino acid linker region (LR). A truncated cel5Z gene was constructed with the addition of a nonsense mutation that removes the C-terminal region of the protein. A truncated Cel5Z protein, consisting of 280 amino acid residues, functioned as a mature enzyme despite the absence of the SP, 11 amino acid CD, LR, and CBD region. In fact, this truncated Cel5Z protein showed an enzymatic activity 80% higher than that of full-length Cel5Z. However, cellulase activity was undetectable in mature Cel5Z proteins truncated to less than 280 amino acids. 相似文献
20.
Forlani G Petrollino D Fusetti M Romanini L Nocek B Joachimiak A Berlicki L Kafarski P 《Amino acids》2012,42(6):2283-2291
Compounds able to interfere with amino acid biosynthesis have the potential to inhibit cell growth. In both prokaryotic and eukaryotic microorganisms, unless an ornithine cyclodeaminase is present, the activity of δ1-pyrroline-5-carboxylate (P5C) reductase is mandatory to proline production, and the enzyme inhibition should result in amino acid starvation, blocking in turn protein synthesis. The ability of some substituted derivatives of aminomethylenebisphosphonic acid and its analogues to interfere with the activity of the enzyme from the human pathogen Streptococcus pyogenes was investigated. Several compounds were able to suppress activity in the micromolar range of concentrations, with a mechanism of uncompetitive type with respect to the substrate P5C and non-competitive with respect to the electron donor NAD(P)H. The actual occurrence of enzyme inhibition in vivo was supported by the effects of the most active derivatives upon bacterial growth and free amino acid content. 相似文献