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Linear Peptides (linear + peptide)
Selected AbstractsImproved Auxiliary for the Synthesis of Medium-Sized Bis(lactams)EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 2 2008Jasper Springer Abstract Our auxiliary-based method for the synthesis of bis(lactams) has been optimized. A novel auxiliary is described that is inserted in the backbone of a linear peptide facilitating the mutually reactive terminal groups to approach one another for a cyclization reaction. A subsequent ring contraction mechanism leads to the bis(lactams) with the remainings of the auxiliary still attached. Functionalized seven- and eight-membered bis(lactams) have been prepared that are difficult to access using traditional methods. Removal of the auxiliary from the bis(lactams) has been described with the possible side reactions that can occur.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Synthesis of the C -terminal domain of the tissue inhibitor of metalloproteinases-1(TIMP-1)JOURNAL OF PEPTIDE SCIENCE, Issue 7 2003József Bódi Abstract According to recent investigations, the C -terminal domain of the tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) is responsible for some biological effects that are independent of the enzyme-inhibiting effect of the N -terminal domain of the molecule. The C -terminal domain has been prepared for structure,biological activity investigations. After the chemical synthesis and the folding of the linear peptide, LC-MS and MALDI-MS analysis revealed that two isomers with different disulphide bond arrangements were formed. Since more than 30 folding experiments resulted in products with a very similar HPLC-profile, it was concluded that in the absence of the TIMP-1 N -terminal domain no entirely correct folding of the C -terminal domain occurred. Furthermore, it was observed that, in spite of several purification steps, mercury(II) ions were bound to the 6SH-linear peptide; it was demonstrated,using disulphide bonded TIMP-1(Cys145 -Cys166) as a model,that mercury(II) ions can cause peptide degradation at pH 7.8 as well as in 0.1% trifluoroacetic acid. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd. [source] Determination of the structure of a hybrid between 2-(1,4-benzoquinone)acetic acid and a linear peptide by electrospray ionization mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 3 2006Antonio Salgado First page of article [source] Antibacterial peptides: basic facts and emerging conceptsJOURNAL OF INTERNAL MEDICINE, Issue 3 2003H. G. Boman Abstract., Boman HG (Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden). Antibacterial peptides: basic facts and emerging concepts (Review). J Intern Med 2003; 254: 197,215. Antibacterial peptides are the effector molecules of innate immunity. Generally they contain 15,45 amino acid residues and the net charge is positive. The cecropin type of linear peptides without cysteine were found first in insects, whilst the defensin type with three disulphide bridges were found in rabbit granulocytes. Now a database stores more than 800 sequences of antibacterial peptides and proteins from the animal and plant kingdoms. Generally, each species has 15,40 peptides made from genes, which code for only one precursor. The dominating targets are bacterial membranes and the killing reaction must be faster than the growth rate of the bacteria. Some antibacterial peptides are clearly multifunctional and an attempt to predict this property from the hydrophobicity of all amino acid side chains are given. Gene structures and biosynthesis are known both in the fruit fly Drosophila and several mammals. Humans need two classes of defensins and the cathelicidin-derived linear peptide LL-37. Clinical cases show that deficiencies in these peptides give severe symptoms. Examples given are morbus Kostmann and atopic allergy. Several antibacterial peptides are being developed as drugs. [source] Structure investigation of Maltacine C1a, C1b, C2a and C2b,cyclic peptide lactones of the Maltacine complex from Bacillus subtilisJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 10 2005Gunnar Hagelin Abstract A new complex of cyclic peptide lactone antibiotics from Bacillus subtilis, which we named Maltacines, has recently been described. The structure elucidation of four of them is reported in this paper. The amino acid sequences and structures of the peptides were found by MSn of the ring-opened linear peptides, which gave uninterrupted sequences of Bn and Y,n ions. The identities of three unknown residues in the sequences were solved by a combination of derivatisation with phenylisothiocyanate (PITC), high-resolution mass spectrometry and H/D exchange. The nature and position of the cyclic structure was disclosed by a chemo-selective ring opening with Na18OH and was found to be a lactone formed between a hydroxyl of residue number 4 and the C -terminal amino acid number 12. For verification of the structure of the B2+ ion, peptides with different combinations of P/Q and P/K at the N -terminus were synthesised. The structure of the four peptides were found to be: C1a and C2a: cyclo-4,12(P-Q-Y-Adip-V-E-T-Y-Orn-103-Y-I-OH) and C1b/C2b: cyclo-4,12(P-Q-Y-Adip-V-E-T-Y-K-103-Y-I-OH). Adip = aminodihydroxy pentanoic acid. Copyright © 2005 John Wiley & Sons, Ltd. [source] Structure investigation of Maltacine D1a, D1b and D1c,cyclic peptide lactones of the Maltacine complex from Bacillus subtilisJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 10 2005Gunnar Hagelin Abstract A new complex of cyclic peptide lactone antibiotics from Bacillus subtilis, which we named Maltacines has recently been described. The structure elucidation of three of them is reported in this paper. The amino acid sequences and structures of the peptides were found by MSn of the ring-opened linear peptides that gave uninterrupted sequences of Bn and Y,n ions. The identities of four unknown residues in the sequences were solved by a combination of derivatisation with phenylisothiocyanate (PITC), high-resolution mass spectrometry and H/D exchange. The nature and position of the cyclic structure was disclosed by a chemo-selective ring opening with Na18OH and was found to be a lactone formed between a hydroxyl of residue number 4 and the C -terminal amino acid number 12. For verification of the structure of the B2+ ion, peptides with different combinations of P/Q and P/K at the N -terminus were synthesized. The structures of the four peptides is tentatively suggested to be: D1a: cyclo(4,12)-P-Q-Y-Adip-A-E-T-Y-Orn-HGly-Y-I-OH, D1b: cyclo(4,12)-P-Q-Y-Adip-A-E-T-Y-Orn-S-Y-I-OH and D1c: cyclo(4,12)-P-Q-Y-Adip-A-E-T-Y-K-S-Y-I-OH. Adip = aminodihydroxy pentanoic acid and HGly = hydroxyglycine. Copyright © 2005 John Wiley & Sons, Ltd. [source] Characterization of a human monoclonal antibody obtained after immunization with plasma vaccine and a booster with recombinant-DNA hepatitis B vaccineJOURNAL OF MEDICAL VIROLOGY, Issue 3 2002R.A. Heijtink Abstract A human monoclonal antibody type IgG4, designated 1Ff4, was obtained by Epstein Barr virus transformation of peripheral blood lymphocytes from a hepatitis B vaccinee (HB-VAX: plasma-derived vaccine) after one boost of yeast recombinant DNA derived vaccine (Engerix-B). 1Ff4 binds preferentially to HBsAg/adw2 and HBsAg/ayw1. In binding experiments, it competes with antibodies induced by vaccination with HB-VAX-DNA (yeast recombinant) and HB-VAX (plasma-derived vaccine). 1Ff4 competes in part with a monoclonal antibody for the w/r region. Partial inhibition of binding of HBsAg/adw2 to solid phase anti-HBs was detected, resembling inhibition obtained using other human monoclonal specific for the "a"-loop. 1Ff4 does not bind to linear peptides covering the two "a"-loops or to an adw2/G145R mutant, its binding to wild type HBsAg strongly depends on the presence of disulphide bonds. In a large series of HBsAg-positive samples from an endemic area, 1Ff4 antibodies were successfully used to discriminate between an adw2 and an adrq+ strain. The characterisation of 1Ff4 and other human monoclonal anti-HBs antibodies may help to understand the fine specificity of protective antibodies elicited by immunization. J. Med. Virol. 66:304-311, 2002. © 2002 Wiley-Liss, Inc. [source] Modeling an active conformation for linear peptides and design of a competitive inhibitor for HMG-CoA reductaseJOURNAL OF MOLECULAR RECOGNITION, Issue 4 2008Valeriy V. Pak Abstract This study presents an approach that can be used to search for lead peptide candidates, including unconstrained structures in a recognized sequence. This approach was performed using the design of a competitive inhibitor for 3-hydroxy-3-methylglutaryl CoA reductase (HMGR). In a previous design for constrained peptides, a head-to-tail cyclic structure of peptide was used as a model of linear analog in searches for lead peptides with a structure close to an active conformation. Analysis of the conformational space occupied by the peptides suggests that an analogical approach can be applied for finding a lead peptide with an unconstrained structure in a recognized sequence via modeling a cycle using fixed residues of the peptide backbone. Using the space obtained by an analysis of the bioactive conformations of statins, eight cyclic peptides were selected for a peptide library based on the YVAE sequence as a recognized motif. For each cycle, the four models were assessed according to the design criterion ("V" parameter) applied for constrained peptides. Three cyclic peptides (FGYVAE, FPYVAE, and FFYVAE) were selected as lead cycles from the library. The linear FGYVAE peptide (IC50,=,0.4,µM) showed a 1200-fold increase the inhibitory activity compared to the first isolated LPYP peptide (IC50,=,484,µM) from soybean. Experimental analysis of the modeled peptide structures confirms the appropriateness of the proposed approach for the modeling of active conformations of peptides. Copyright © 2008 John Wiley & Sons, Ltd. [source] Conformational study on glycosylated asparagine-oligopeptides by NMR spectroscopy and molecular dynamics calculationsJOURNAL OF PEPTIDE SCIENCE, Issue 8 2005Stefania Mazzini Abstract The conformational properties of the homo oligomers of increasing chain length Boc-(Asn)n -NHMe (n = 2, 4, 5), (GlcNAc-,-Asn)n -NHMe (n = 2, 4, 5, 8) and Boc-[GlcNAc(Ac)3 -,-Asn]n -NHMe (n = 2, 4, 5) were studied by using NOE experiments and molecular dynamic calculations (MD). Sequential NOEs and medium range NOEs, including (i,i+2) interactions, were detected by ROESY experiments and quantified. The calculated inter-proton distances are longer than those characteristic of ,-turn secondary structures. Owing to the large conformational motions expected for linear peptides, MD simulations were performed without NMR constraints, with explicit water and by applying different treatments of the electrostatic interactions. In agreement with the NOE results, the simulations showed, for all peptides, the presence of both folded and unfolded structures. The existence of significant populations of ,-turn structures can be excluded for all the examined compounds, but two families of structures were more often recognized. The first one with sinusoidal or S-shaped forms, and another family of large turns together with some more extended conformations. Only the glycosylated pentapeptide shows in vacuo a large amount of structures with helical shaped form. The results achieved in water and in DMSO are compared and discussed, together with the effect of the glycosylation. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd. [source] Structural characterization of cyclic kallidin analogues in DMSO by nuclear magnetic resonance and molecular dynamicsJOURNAL OF PEPTIDE SCIENCE, Issue 1 2005Elisabetta Schievano Abstract The conformational properties in DMSO of two head-to-tail cyclic analogues of kallidin ([Lys0]-bradykinin, KL) as well as those of the corresponding linear peptides were studied by NMR and molecular dynamics (MD) simulations. The modifications in the sequence were introduced at position 6, resulting in the four peptides, [Tyr6]-KL (YKL), [Trp6]-KL (WKL), cyclo-([Tyr6]-KL) (YCKL) and cyclo-([Trp6]-KL) (WCKL). The linear WKL analogue was significantly more potent than kallidin on rat duodenum preparations, whereas YKL was significantly less potent. Both cyclic peptides, YCKL and WCKL displayed similar activity, lower than that of the linear analogues and also of cyclo-KL. The two linear analogues display high conformational flexibility in DMSO. In the predominant conformer, for both peptides, all three X-Pro bonds adopt a trans configuration. Three out of four conformers present in YCKL and WCKL were completely assigned. The configurations at the X-Pro bonds are the same for the two analogues. All cyclic conformers show a cis configuration in at least one X-Pro bond and always opposite configuration for the two consecutive X-Pro bonds. The NOE-restrained MD calculations resulted in the detection of several elements of secondary structure in each of the conformers. Such elements are described and their possible relevance to biological activity is discussed. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd. [source] Solution structure of nociceptin peptidesJOURNAL OF PEPTIDE SCIENCE, Issue 9 2002Pietro Amodeo Abstract Peptides embedded in the sequence of pre-pro-nociceptin, i.e. nociceptin, nocistatin and orphanin FQ2, have shed light on the complexity of the mechanisms involving the peptide hormones related to pain and have opened up new perspectives for the clinical treatment of pain. The design of new ligands with high selectivity and bioavailability, in particular for ORL1, is important both for the elucidation and control of the physiological role of the receptor and for their therapeutic importance. The failure to obtain agonists and antagonists when using, for nociceptin, the same substitutions that are successful for opioids, and the conformational flexibility of them all, justify systematic efforts to study the solution conformation under conditions as close as possible to their natural environment. Structural studies of linear peptides in solution are hampered by their high flexibility. A direct structural study of the complex between a peptide and its receptor would overcome this difficulty, but such a study is not easy since opioid receptors are membrane proteins. Thus, conformational studies of lead peptides in solution are still important for drug design. This review deals with conformational studies of natural pre-nociceptin peptides in several solvents that mimic in part the different environments in which the peptides exert their action. None of the structural investigations yielded a completely reliable bioactive conformation, but the global conformation of the peptides in biomimetic environments can shed light on their interaction with receptors. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd. [source] Solid-phase synthesis of cyclic analogues related to the hypoglycaemic peptide hGH[6,13]: Comparison of two i,i+4 lactam cyclization proceduresJOURNAL OF PEPTIDE SCIENCE, Issue 10 2001Vittoria Cavallaro Abstract The use of 1,3-diisopropylcarbodiimide (DIC) for the synthesis of cyclic analogues of the hypoglycaemic peptide fragment derived from the N -terminus of human growth hormone (hGH), namely hGH[6,13], is described. Different strategies were examined to achieve improved yields for the on resin side-chain to side-chain cyclization of the corresponding linear peptides containing reverse , - turn motifs. When compared with the more reactive Castro's reagent, the results confirm that DIC in the presence of HOBt can be successfully employed to minimize the formation of intermolecular oligomeric by-products associated with the preparation of cyclic hGH[6,14] peptide analogues based on an i,(i+4)Lys,Glu or Glu,Lys cyclization strategy. Copyright © 2001 European Peptide Society and John Wiley & Sons, Ltd. [source] Highly potent side-chain to side-chain cyclized enkephalin analogues containing a carbonyl bridge: synthesis, biology and conformationJOURNAL OF PEPTIDE SCIENCE, Issue 3 2001Danuta Pawlak Abstract Six novel cyclic enkephalin analogues have been synthesized. Cyclization of the linear peptides containing basic amino acid residues in position 2 and 5 was achieved by treatment with bis(4-nitrophenyl)carbonate. It was found that some of the compounds exibit unusually high µ -opioid activity in the guinea pig ileum (GPI) assay. The 18-membered analogue cyclo(N,,N,, -carbonyl-,,-Lys2,Dap5)enkephalinamide turned out to be one of the most potent µ-agonists reported so far. NMR spectra of the peptides were recorded and structural parameters were determined. The conformational space was exhaustively examined for each of them using the electrostatically driven Monte Carlo method. Each peptide was finally described as an ensemble of conformations. A model of the bioactive conformation of this class of opioid peptides was proposed. Copyright © 2001 European Peptide Society and John Wiley & Sons, Ltd. [source] Mass spectrometric investigation of Maltacines E1a and E1b,two members of the Maltacine family of peptide antibioticsRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 24 2005Gunnar Hagelin We have recently described the discovery of the Maltacines,a new family of cyclic peptide antibiotics from Bacillus subtilis. In this paper the mass spectrometric characterisation of two of the members is reported. A chemoselective ring opening with base to give the linear peptides was necessary before mass spectrometric characterisation could be performed. MSn of the singly and doubly charged protonated molecules gave uninterrupted series of Bn and Y,n ions that allowed determination of the amino acid sequence. By using a combination of derivatisation with phenylisothiocyanate (PITC), high-resolution mass spectrometry and H/D exchange, the identities of three unknown residues were determined. The nature and position of the cyclic structure were disclosed by a chemoselective ring opening with Na18OH and it was found to be a lactone formed between a hydroxyl of residue number 4 and the C-terminal amino acid number 12. Peptides with different combinations of P/Q and P/K at the N-terminus were synthesised to verify the sequence of the N-terminal B2 ion. The structure of the two peptides is proposed to be: E1a: cyclo-4,12(P-Q-Y-Adip-V-E-T-Y-Orn-S-Y-I-OH) and E1b: cyclo-4,12(P-Q-Y-Adip-V-E-T-Y-K-S-Y-I-OH). Adip,=,(2-amino-4,5-dihydroxypentanoic acid). Copyright © 2005 John Wiley & Sons, Ltd. [source] Rheumatoid arthritis,specific autoantibodies to peptidyl arginine deiminase type 4 inhibit citrullination of fibrinogenARTHRITIS & RHEUMATISM, Issue 1 2010Isabelle Auger Objective Autoantibodies to citrullinated proteins are specific for rheumatoid arthritis (RA) and recognize epitopes centered by citrulline, a posttranslationally modified form of arginine. Peptidyl arginine deiminase type 4 (PAD-4), the enzyme that converts arginine into citrulline, is in itself a target for RA-specific autoantibodies. This study was undertaken to assess whether anti,PAD-4 autoantibodies interfere with citrullination in vitro in patients with RA, and to identify peptide targets of anti,PAD-4 antibodies that can activate or inhibit citrullination. Methods To test whether autoantibodies to PAD-4 influence citrullination, an in-house citrullination assay was developed using purified autoantibodies to PAD-4. To map B cell epitopes on PAD-4, 65 overlapping 20-mer peptides encompassing the entire PAD-4 were analyzed for their reactivity in RA sera. Results Autoantibodies to PAD-4 inhibited PAD-4,mediated citrullination. Three linear peptides on PAD-4 were recognized almost uniquely by PAD-4 autoantibodies in the sera of patients with RA. One peptide was located in the N-terminal, calcium-binding domain of PAD-4, while 2 other peptides were located in the C-terminal, substrate-binding domain of PAD-4. Conclusion Autoantibodies to PAD-4 inhibit in vitro citrullination of fibrinogen by PAD-4. Most anti,PAD-4,positive sera recognize peptides located both in the N-terminal domain (211,290) and the C-terminal domain (601,650) of PAD-4. [source] | |||||||||||||