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Cyclic Peptides (cyclic + peptide)
Selected AbstractsConformational Consequences of Regio- and Stereoselective Disulfide Bridge Oxidation in a Cyclic PeptideCHEMBIOCHEM, Issue 1 2008Miroslav Male Synthesis of thiosulfinates. A thiosulfinate moiety was introduced into a cyclic peptide by regio- and stereoselective disulfide-bridge oxidation of S2,S6 -cyclo(H-Gly-Cys-Ser-Pro-Ala-Cys-Gly-OH). The CD, FTIR and NMR spectroscopic data demonstrated drastic changes in the peptide secondary structure upon oxidation of the Cys6 sulfur atom, while oxidation of the Cys2 sulfur atom caused only minor structure perturbations. [source] Synthesis of a New Cyclic Peptide, Pseudostellarin GCHEMINFORM, Issue 47 2004Boja Poojary Abstract For Abstract see ChemInform Abstract in Full Text. [source] Synthesis of Cyclic Peptides by Photochemical Decarboxylation of N -Phthaloyl Peptides in Aqueous SolutionHELVETICA CHIMICA ACTA, Issue 12 2002The synthesis of a variety of cyclic peptides from N -phthaloyl-protected di-, tri-, tetra-, and pentapeptides with different aminocarboxylic acid tethers by photodecarboxylation , initiated by intramolecular electron transfer , has been explored in aqueous media. The progress and the chemoselectivity of the follow-up processes after CO2 extrusion were traced by the respective pH/time-profiles, as well as by the overall change in pH after completion of the reaction. The competition between cyclization and simple oxidative decarboxylation depends on spacer length and geometry, H-bonding interaction between the electron accepting phthalimide CO groups and amide H-atoms, as well as the geometric reorganization coupled with the radical combination step and the formation of the lactam rings. With progressing reaction, hydrolysis of the phthalimide chromophore becomes an increasingly important side reaction due to the constant increase in pH. The use of phosphate-buffered aqueous media consequently improved the cyclization yields. The ground-state interactions between amide groups and the terminal COO, group with the imide CO groups were studied for the model system [N -(phthaloyl)glycyl]sarcosine (1) by NMR spectroscopy where the amide (E/Z)-equilibrium depends on the presence of carboxylate vs. free carboxylic acid, demonstrating the role of H-bonding and metal coordination. [source] ChemInform Abstract: Pompanopeptins A and B, New Cyclic Peptides from the Marine Cyanobacterium Lyngbya confervoides.CHEMINFORM, Issue 37 2008Susan Matthew Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Synthesis of Cyclic Peptides Constrained with Biarylamine Linkers Using Buchwald,Hartwig C,N Coupling.CHEMINFORM, Issue 4 2007V. Balraju Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Myriastramides A,C, New Modified Cyclic Peptides from the Philippines Marine Sponge Myriastra clavosa.CHEMINFORM, Issue 9 2004Karen L. Erickson No abstract is available for this article. [source] Synthesis of Small Cyclic Peptides via Intramolecular Heck ReactionsCHEMINFORM, Issue 15 2003P. Rajamohan Reddy Abstract For Abstract see ChemInform Abstract in Full Text. [source] ChemInform Abstract: Synthesis of Cyclic Peptides by Ring-Closing Metathesis.CHEMINFORM, Issue 5 2001John F. Reichwein Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Folding Control in Cyclic Peptides through N-Methylation Pattern Selection: Formation of Antiparallel ,-Sheet Dimers, Double Reverse Turns and Supramolecular Helices by 3,,, Cyclic PeptidesCHEMISTRY - A EUROPEAN JOURNAL, Issue 7 2008Manuel Amorín Dr. Abstract Peptide foldamers constitute a growing class of nanomaterials with potential applications in a wide variety of chemical, medical and technological fields. Here we describe the preparation and structural characteristics of a new class of cyclic peptide foldamers (3,,,-CPs) that, depending on their backbone N-methylation patterns and the medium, can either remain as flat rings that dimerize through arrays of hydrogen bonds of antiparallel ,-sheet type, or can fold into twisted double reverse turns that, in the case of double ,-turns, associate in nonpolar solvents to form helical supramolecular structures. A 3,,,-CP consists of a number of multiples of a repeat unit made up of four amino acid residues of alternating chirality: three corresponding to ,-amino acids and one to a ,-amino acid (a cis -3-aminocycloalkanecarboxylic acid). [source] Inhibition of Human Leukocyte Elastase by Brunsvicamides,A,C: Cyanobacterial Cyclic PeptidesCHEMMEDCHEM, Issue 9 2009Mihiret Cyanobacterial cyclic peptides, brunsvicamides,A,C, were evaluated as inhibitors of human leukocyte elastase (HLE), and subsequently tested against a panel of proteases and two serine esterases. Brunsvicamides,A,C were found to be highly selective for HLE. [source] Carbohydrate-Based VEGF InhibitorsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 36 2007Tobias Haag Abstract Cyclic peptide,carbohydrates (compounds 1a,c, 2, 33, 34) were designed and synthesized to act as mimetics of loop 2 of the proangiogenic molecule vascular endothelial growth factor D (VEGF-D). The mimetics were designed to inhibit dimerization of the receptors (VEGFR-2 and VEGFR-3) by VEGF-D, and thus have the potential to inhibit angiogenesis. To this end, in the previously described cyclic octapeptide CNEESLIC and the cyclic nonapeptide CGNEESLIC inhibitors derived from VEGF-D loop 2, the NEES tetrapeptide residue was replaced by a carbohydrate scaffold having the amino acid side chain mimics in positions proposed by modeling studies. Attachment of the additional amino acids using the Fmoc technology, then formation of the cyclic disulfides, and finally total deprotection afforded the target molecules of which 2 and 34 showed an ability to inhibit the biological activity of VEGF-D through VEGFR-2 in cell-based assays, albeit at high mimetic concentration.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Cyclic peptides selected by phage display mimic the natural epitope recognized by a monoclonal anti-colicin A antibodyJOURNAL OF PEPTIDE SCIENCE, Issue 11 2004Stephane Coulon Abstract A 10-mer random peptide library displayed on filamentous bacteriophage was used to determine the molecular basis of the interaction between the monoclonal anti-colicin A antibody 1C11 and its cognate epitope. Previous studies established that the putative epitope recognized by 1C11 antibody is composed of amino acid residues 19,25 (RGSGPEP) of colicin A. Using the phage display technique it was confirmed that the epitope of 1C11 antibody was indeed restricted to residues 19,25 and the consensus motif RXXXPEP was identified. Shorter consensus sequences (RXXPEP, RXXEP, KXXEP) were also selected. It was also demonstrated that the disulfide bond found in one group of the selected peptides was crucial for 1C11 antibody recognition. It was shown that cyclization of the peptides by disulfide bond formation could result in a structure that mimics the natural epitope of colicin A. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd. [source] Comparison of the contractile responses of human coronary bypass grafts and monkey arteries to human urotensin-IIFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2001J. Paysant Human urotensin-II (hU-II) is a cyclic peptide recently cloned in humans and present in human cardiac tissue and human arteries. The effects of hU-II were studied on human coronary bypass grafts in vitro. In three out of eight human mammary arteries, and two out of three human radial arteries, hU-II caused contraction; human saphenous veins did not respond to hU-II. When it exists, the contraction slowly develops and has a low-to-moderate intensity. All radial arteries obtained from young healthy non-human primates contracted strongly to hU-II. [source] Effect of Urotensin II on PC12 Rat Pheochromocytoma CellsJOURNAL OF NEUROENDOCRINOLOGY, Issue 2 2010Y. Aita Urotensin II (U-II), initially identified as a cyclic peptide from fish urophysis, acts both as a strong vasoconstrictor and vasodilator in the vasculature via its receptor, G-protein coupled receptor 14. In addition, U-II and its receptor are co-expressed in the adrenal medulla, as well as in human pheochromocytomas, suggesting that this peptide may have some function in chromaffin cells. However, the precise role of U-II in these cells is unknown. In the present study, we initially demonstrate that U-II and its receptors mRNA are co-expressed in the rat pheochromocytoma cell line PC12. Moreover, U-II has not effect on tyrosine hydroxylase (TH), the rate-limiting enzyme involved in the biosynthesis of catecholamine, in terms of enzyme activity or at the mRNA level. However, U-II does induce an increase in the phosphorylation of TH specifically at Ser31 without affecting phosphorylation at the two other sites (Ser19 and Ser40). U-II also markedly activates extracellular signal-regulated kinases (ERKs) and p38, but not Jun N-terminal kinase. Blockade of the epidermal growth factor (EGF) receptor by AG1478 significantly reduces activation of ERK, suggesting that EGF receptor transactivation could act upstream of the ERK pathway in PC12 cells. Furthermore, U-II significantly increases dopamine secretion from PC12 cells. Finally, we show that U-II induced significant DNA synthesis in a ERKs and P38 mitogen-activated protein kinase-dependent manner. The results obtained indicate that U-II may exert its effects as a neuromodulator in chromaffin cells. [source] Thiocarbamate-linked peptides by chemoselective peptide ligationJOURNAL OF PEPTIDE SCIENCE, Issue 12 2008Soizic Besret Abstract Peptide chemical ligation chemistries, which allow the chemoselective coupling of unprotected peptide fragments, are useful tools for synthesizing native polypeptides or unnatural peptide-based macromolecules. We show here that the phenylthiocarbonyl group can be easily introduced into peptides on , or , amino groups using phenylthiochloroformate and standard solid-phase method. It reacts chemoselectively with cysteinyl peptides to give an alkylthiocarbamate bond. S,N -shift of the alkylaminocarbonyl group from the Cys side chain to the ,-amino group did not occur. The method was used for linking two peptide chains through their N -termini, for the synthesis of a cyclic peptide or for the synthesis of di- or tetravalent multiple antigenic peptides (MAPs). Thiocarbamate ligation is thus complementary to thioether, thioester or disulfide ligation methods. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd. [source] Transition metal complexes of a cyclic pseudo hexapeptide: synthesis, complex formation and catalytic activities,,JOURNAL OF PEPTIDE SCIENCE, Issue 9 2008Huong Ngyen Abstract To contribute to a better understanding of metalloenzymes, we studied ion selectivity, complex formation tendencies and catalytic activities of linear and cyclic pseudopeptides. In this contribution, a linear and cyclic pseudo hexapeptide is described. The complex with transition metal ions and the sequence were designed using the programme COSMOS. Different routes of solid-phase synthesis were performed and compared using anchoring by C -terminus or a His side chain, using preformed pseudodipeptide building units or formation of N -functionalized peptide bond during stepwise assembly. The different strategies were compared regarding cyclization tendency, yield and purity. Side-chain anchoring to solid support favours the cyclization but leads to the formation of difficult to separate dioxopiperazine. Both routes require preformed building units. Complex-formation tendencies and selectivity for certain bivalent transition metal ions were experimentally estimated and compared to ones predicted theoretically. CD measurements indicate conformational changes by complex formation with different metal ions. Catalytic activities on oxidation of catechol and hydrolysis of bis-phosphate esters by some metal complexes of linear and cyclic peptide show only low catalytic activities compared to other model peptides and related metalloenzymes. The preference of the cyclic peptide for complexation of Ni2+ corresponds well to the predictions of COSMOS-NMR force field calculations. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd. [source] Structural studies and model membrane interactions of two peptides derived from bovine lactoferricinJOURNAL OF PEPTIDE SCIENCE, Issue 7 2005Leonard T. Nguyen Abstract The powerful antimicrobial properties of bovine lactoferricin (LfcinB) make it attractive for the development of new antimicrobial agents. An 11-residue linear peptide portion of LfcinB has been reported to have similar antimicrobial activity to lactoferricin itself, but with lower hemolytic activity. The membrane-binding and membrane-perturbing properties of this peptide were studied together with an amidated synthetic version with an added disulfide bond, which was designed to confer increased stability and possibly activity. The antimicrobial and cytotoxic properties of the peptides were measured against Staphylococcus aureus and Escherichia coli and by hemolysis assays. The peptides were also tested in an anti-cancer assay against neuroblastoma cell lines. Vesicle disruption caused by these LfcinB derivatives was studied using the fluorescent reporter molecule calcein. The extent of burial of the two Trp residues in membrane mimetic environments were quantitated by fluorescence. Finally, the solution NMR structures of the peptides bound to SDS micelles were determined to provide insight into their membrane bound state. The cyclic peptide was found to have greater antimicrobial potency than its linear counterpart. Consistent with this property, the two Trp residues of the modified peptide were suggested to be embedded deeper into the membrane. Although both peptides adopt an amphipathic structure without any regular ,-helical or ß-sheet conformation, the 3D-structures revealed a clearer partitioning of the cationic and hydrophobic faces for the cyclic peptide. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd. [source] Synthesis, conformational analysis and biological activities of lanthionine analogs of a cell adhesion modulatorJOURNAL OF PEPTIDE SCIENCE, Issue 2 2001Haitao Li Abstract Cell adhesion is critical for many biological processes, such as hemostasis, wound healing, tumor metastasis and inflammation. Integrins are important mediators of cell adhesion. The integrin ,4,1, also known as VLA-4, is a cell surface receptor involved in inflammation. A cyclic peptide, 1-FCA-Arg-c[Cys-Asp-Thz-Cys]-OH, is a potent antagonist to VLA-4 with an IC50 of 2.4 n,,. In the current study, we synthesized the lanthionine analogs of 1-FCA-Arg-c[Cys-Asp-Thz-Cys]-OH and determined the conformations of both the parent compound and its lanthionine analog in solution by NMR and computer simulations. The lanthionine analog retains its selectivity to VLA-4 with high nanomolar potency. Both molecules adopt similar topological arrangements in their conformations, while some important differences remain in the sulfur bridge region, which may cause the difference in potency. Copyright © 2001 European Peptide Society and John Wiley & Sons, Ltd. [source] Synthesis and chemical stability of a disulfide bond in a model cyclic pentapeptide: Cyclo(1,4)-Cys-Gly-Phe-Cys-Gly-OHJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2006Henry T. He Abstract Many cyclic peptides are formed using a disulfide bond to increase their conformational rigidity; this provides receptor selectivity and increased potency. However, degradation of the disulfide bond in formulation can lead to a loss of structural stability and biological activity of the peptide. Therefore, the objective of this study was to study the stability of peptide 1 (cyclo(1,4)-Cys-Gly-Phe-Cys-Gly-OH). This cyclic peptide was synthesized using Boc strategy via solution-phase peptide synthesis and purified using semi-preparative HPLC. The accelerated stability studies of the cyclic peptide were conducted in buffer solutions at pH 1.0,11.0 with controlled ionic strengths at 70°C. The pH-rate profile shows that the peptide has an optimal stability around pH 3.0 with a V-shape between pH 1.0 and 5.0. Two small plateaus are observed at pH 5.0,7.0 and pH 8.0,10.0, indicating hydrolysis on different ionized forms of the cyclic peptide. One product was observed at acidic pH due to peptide bond hydrolysis at Gly2-Phe3. The number of degradation products increases as the pH increases from neutral to basic, and most of the degradation products at neutral and basic pH are derived from the degradation at the disulfide bond. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:2222,2234, 2006 [source] Synthesis and Controlled Polymerisation of a Novel Gramicidin S AnalogueMACROMOLECULAR RAPID COMMUNICATIONS, Issue 16 2005Lee Ayres Abstract Summary: The controlled polymerisation of a bulky, peptide-based monomer was investigated. The cyclic , -sheet forming decapeptide gramicidin S was modified with a methacrylate handle and subsequently polymerised via atom transfer radical polymerisation (ATRP), to yield a well-defined gramicidin-S-containing polymer. The secondary structure of the peptide moiety was retained within the resulting polymer, as indicated by IR spectroscopy. This is the first example of the use of ATRP to create a synthetic polymer with a cyclic peptide as a side chain. The gramicidin S based monomers synthesised here were then polymerised by ATRP. [source] Structure elucidation and 3D solution conformation of the antibiotic enduracidin determined by NMR spectroscopy and molecular dynamicsMAGNETIC RESONANCE IN CHEMISTRY, Issue 8 2005F. Castiglione Abstract Enduracidin and ramoplanin belong to the large family of cyclodepsipeptide antibiotics, highly effective against Gram-positive bacteria. The primary and 3D solution structure of ramoplanin is already well known, and the primary structure of enduracidin has been determined by a combination of chemical and NMR spectroscopic methods. Both antibiotics share a similar peptide core of 17 amino acids and differ mainly in the length of the acyl chain and the presence of two D -mannose moieties in ramoplanin. Based on the high sequence homology with ramoplanin, the structure in solution of enduracidin is modeled as a cyclic peptide. The tertiary structure thus obtained was refined through molecular dynamics (MD) simulation, in which the interatomic NOE-derived distance restraints were imposed. MD simulations yielded a family of representative 3D structures (RMSD = 0.89), which highlighted a backbone geometry similar to that of ramoplanin in its ,-hairpin arrangement. In contrast, enduracidin displays a different arrangement of the side-chain and of the residues forming the hydrophobic core. Copyright © 2005 John Wiley & Sons, Ltd. [source] Solution structure of the cyclic peptide contryphan-Vn, a Ca2+ -dependent K+ channel modulatorBIOPOLYMERS, Issue 3 2004Tommaso Eliseo Abstract The solution structure of contryphan-Vn, a cyclic peptide with a double cysteine S,S bridge and containing a D -tryptophan extracted from the venom of the cone snail Conus ventricosus, has been determined by NMR spectroscopy using a variety of homonuclear and heteronuclear NMR methods and restrained molecular dynamics simulations. The main conformational features of backbone contryphan-Vn are a type IV ,-turn from Gly 1 to Lys 6 and a type I ,-turn from Lys 6 to Cys 9. As already found in other contryphans, one of the two prolines,the Pro4,is mainly in the cis conformation while Pro7 is trans. A small hydrophobic region probably partly shielded from solvent constituted from the close proximity of side chains of Pro7 and Trp8 was observed together with a persistent salt bridge between Asp2 and Lys6, which has been revealed by the diagnostic observation of specific nuclear Overhauser effects. The salt bridge was used as a restraint in the molecular dynamics in vacuum but without inserting explicit electrostatic contribution in the calculations. The backbone of the unique conformational family found of contryphan-Vn superimposes well with those of contryphan-Sm and contryphan-R. This result indicates that the contryphan structural motif represents a robust and conserved molecular scaffold whose main structural determinants are the size of the intercysteine loop and the presence and location in the sequence of the D -Trp and the two Pro residues. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004 [source] A Novel Cyanobacterial Nostocyclopeptide is a Potent Antitoxin against MicrocystinsCHEMBIOCHEM, Issue 11 2010Jouni Jokela Abstract Cyanobacterial hepatotoxins (microcystins and nodularins) cause numerous animal poisonings worldwide each year and are threats to human health. However, we found that extracts from several cyanobacteria isolates failed to induce hepatotoxicity even if they contained high concentrations of the liver toxin microcystin. The antitoxic activity abolishes all morphological hallmarks of microcystin-induced apoptosis, and therefore invalidates cell-based assays of the microcystin content of bloom-forming cyanobacteria. The antitoxin was purified from a cyanobacterial isolate (Nostoc sp. XSPORK 13A) from the Baltic Sea, and the activity was shown to reside in a novel cyclic peptide of the nostocyclopeptide family (nostocyclopeptide M1, Ncp-M1) that consists of seven amino acids (Tyr1 -Tyr2 - D -HSe3 - L -Pro4 - L -Val5 -(2S,4S)-4-MPr6 -Tyr7; MW=881) with an imino linkage between Tyr1 and Tyr7. Ncp-M1 did not compete with labelled microcystin for binding to protein phosphatase 2A; this explains why the antitoxin did not interfere with phosphatase-based microcystin assays. Currently used agents that interfere with microcystin action, such as inhibitors of ROS formation, microcystin uptake and Cam-kinase activity, are themselves inherently toxic. Since Ncp-M1 is potent and nontoxic it promises to become a useful mechanistic tool as soon as its exact cellular target is elucidated. [source] Genetic Selection of Cyclic Peptide Dam Methyltransferase InhibitorsCHEMBIOCHEM, Issue 2 2008Todd A. Naumann Dr. Let's go round. We report the development of a transposition based genetic selection methodology used to uncover three cyclic peptide inhibitors of the E. coli methyltransferase. The activity of the selected cyclic peptides was confirmed in vivo and in vitro. The IC50 of the most active cyclic peptide (SGWYVRNM, shown in the figure) was comparable to that of the known methyltransferase inhibitor, sinefungin. [source] Conformational Consequences of Regio- and Stereoselective Disulfide Bridge Oxidation in a Cyclic PeptideCHEMBIOCHEM, Issue 1 2008Miroslav Male Synthesis of thiosulfinates. A thiosulfinate moiety was introduced into a cyclic peptide by regio- and stereoselective disulfide-bridge oxidation of S2,S6 -cyclo(H-Gly-Cys-Ser-Pro-Ala-Cys-Gly-OH). The CD, FTIR and NMR spectroscopic data demonstrated drastic changes in the peptide secondary structure upon oxidation of the Cys6 sulfur atom, while oxidation of the Cys2 sulfur atom caused only minor structure perturbations. [source] Design and Synthesis of Cyclopeptide Analogues of the Potent Histone Deacetylase Inhibitor FR235222CHEMMEDCHEM, Issue 10 2007Luigi Gomez-Paloma Prof. Abstract Various structurally modified analogues of FR235222 (1), a natural tetrapeptide inhibitor of mammalian histone deacetylases, were prepared in a convergent approach. The design of the compounds was aimed to investigate the effect of structural modifications of the tetrapeptide core involved in enzyme binding in order to overcome some synthetic difficulties connected with the natural product 1. The modifications introduced could also help identify key structural features involved in the mechanism of action of these compounds. The prepared molecules were subjected to in,vitro pharmacological tests, and their potency was tested on cultured cells. Two of the components of the array were found to be more potent than the parent compound 1 and almost as efficient as trichostatin,A (TSA). These results demonstrate that it is possible to synthesize highly active cyclic tetrapeptides using commercially available amino acids (with the exception of 2-amino-8-oxodecanoic acid, Ahoda). The nature of the residue in the second position of the cyclic peptide and the stereochemistry of the Ahoda tail are important for the inhibitory activity of this class of cyclic tetrapeptide analogues. [source] Synthesis of Cyclic Peptides by Photochemical Decarboxylation of N -Phthaloyl Peptides in Aqueous SolutionHELVETICA CHIMICA ACTA, Issue 12 2002The synthesis of a variety of cyclic peptides from N -phthaloyl-protected di-, tri-, tetra-, and pentapeptides with different aminocarboxylic acid tethers by photodecarboxylation , initiated by intramolecular electron transfer , has been explored in aqueous media. The progress and the chemoselectivity of the follow-up processes after CO2 extrusion were traced by the respective pH/time-profiles, as well as by the overall change in pH after completion of the reaction. The competition between cyclization and simple oxidative decarboxylation depends on spacer length and geometry, H-bonding interaction between the electron accepting phthalimide CO groups and amide H-atoms, as well as the geometric reorganization coupled with the radical combination step and the formation of the lactam rings. With progressing reaction, hydrolysis of the phthalimide chromophore becomes an increasingly important side reaction due to the constant increase in pH. The use of phosphate-buffered aqueous media consequently improved the cyclization yields. The ground-state interactions between amide groups and the terminal COO, group with the imide CO groups were studied for the model system [N -(phthaloyl)glycyl]sarcosine (1) by NMR spectroscopy where the amide (E/Z)-equilibrium depends on the presence of carboxylate vs. free carboxylic acid, demonstrating the role of H-bonding and metal coordination. [source] Chemical synthesis and biosynthesis of the cyclotide family of circular proteinsIUBMB LIFE, Issue 9 2006Sunithi Gunasekera Abstract Cyclotides are a recently discovered class of proteins that have a characteristic head-to-tail cyclized backbone stabilized by a knotted arrangement of three disulfide bonds. They are exceptionally resistant to chemical, enzymatic and thermal treatments because of their unique structural scaffold. Cyclotides have a range of bio-activities, including uterotonic, anti-HIV, anti-bacterial and cytotoxic activity but their insecticidal properties suggest that their natural physiological role is in plant defense. They are genetically encoded as linear precursors and subsequently processed to produce mature cyclic peptides but the mechanism by which this occurs remains unknown. Currently most cyclotides are obtained via direct extraction from plants in the Rubiaceae and Violaceae families. To facilitate the screening of cyclotides for structure-activity studies and to exploit them in drug design or agricultural applications a convenient route for the synthesis of cyclotides is vital. In this review the current chemical, recombinant and biosynthetic routes to the production of cyclotides are discussed. iubmb Life, 58: 515-524, 2006 [source] Do collisions inside the collision cell play a relevant role in CID-LIFT experiments?,JOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 1 2007Gloriano Moneti Abstract Collision experiments are a valid approach to characterize the ionic species generated by matrix assisted laser desorption ionization (MALDI). When a time-of-flight analyzer is employed, three different approaches are available for these experiments: the postsource decay (PSD), the LIFT and the MALDI-TOF/TOF. The last two are of particular interest because of the overcoming of the PSD problems related to mass calibration of the product ion spectra. Experiments performed by LIFT on linear or cyclic peptides, in presence or in absence of collision gas in the collision cell, gave evidence of an unexpected behavior: the two spectra were practically superimposable, and in the former case only a few new fragmentation channels were activated with low yield. These results mean that the selected ion exhibits a large amount of internal energy, capable of promoting fragmentation processes in the time window corresponding to the flight time between ion source and the acceleration electrode placed after the collision cell. Experiments performed by varying the plume density show that this internal energy uptake occurs in the expanding plume, through multiple collisions. The LIFT data have been compared with those achieved by collisions of ESI-generated [MH]+ ions of angotensin II performed under ,in-source' conditions and by triple-quadrupole experiments. The obtained results show a strong similarity among the spectra, indicating that the internal energy uptake in a MALDI source is comparable with that of 40-eV ions colliding with Ar in a triple-quadrupole instrument. Copyright © 2006 John Wiley & Sons, Ltd. [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] | |||||||||||||||||||||||||||||||