The journal of peptide research : official journal of the American Peptide Society最新文献

{"title":"Structure-activity relationships of arodyn, a novel acetylated kappa opioid receptor antagonist.","authors":"M A Bennett,&nbsp;T F Murray,&nbsp;J V Aldrich","doi":"10.1111/j.1399-3011.2005.00216.x","DOIUrl":"https://doi.org/10.1111/j.1399-3011.2005.00216.x","url":null,"abstract":"<p><p>We previously reported that the novel dynorphin A (Dyn A, Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile-Arg-Pro-Lys-Leu-Lys-Trp-Asp-Asn-Gln) analog arodyn (Ac[Phe(1,2,3),Arg(4),d-Ala(8)]Dyn A-(1-11)NH(2), Bennett, M.A., Murray, T.F. & Aldrich, J.V. (2002) J. Med. Chem. vol. 45, pp. 5617-5619) is a kappa opioid receptor-selective peptide [K(i)(kappa) = 10 nm, K(i) ratio (kappa/mu/delta) = 1/174/583] which exhibits antagonist activity at kappa opioid receptors. In this study, a series of arodyn analogs was prepared and evaluated to explore the structure-activity relationships (SAR) of this peptide; this included an alanine scan of the entire arodyn sequence, sequential isomeric d-amino acid substitution in the N-terminal 'message' sequence, NMePhe substitution individually in positions 1-3, and modifications in position 1. The results for the Ala-substituted derivatives indicated that Arg(6) and Arg(7) are the most important residues for arodyn's nanomolar binding affinity for kappa opioid receptors. Ala substitution of the other basic residues (Arg(4), Arg(9) and Lys(11)) resulted in lower decreases in affinity for kappa opioid receptors (three- to fivefold compared with arodyn). Of particular interest, while [Ala(10)]arodyn exhibits similar kappa opioid receptor binding as arodyn, it displays higher kappa vs. mu opioid receptor selectivity [K(i) ratio (kappa/mu) = 1/350] than arodyn because of a twofold loss in affinity at mu opioid receptors. Surprisingly, the Tyr(1) analog exhibits a sevenfold decrease in kappa opioid receptor affinity, indicating that arodyn displays significantly different SAR than Dyn A; [Tyr(1)]arodyn also unexpectedly exhibits inverse agonist activity in the adenylyl cyclase assay using Chinese hamster ovary cells stably expressing kappa opioid receptors. Substitution of NMePhe in position 1 gave [NMePhe(1)]arodyn which exhibits high affinity [K(i)(kappa) = 4.56 nm] and exceptional selectivity for kappa opioid receptors [K(i) ratio (kappa/mu/delta) = 1/1100/>2170]. This peptide exhibits antagonistic activity in the adenylyl cyclase assay, reversing the agonism of 10 nm Dyn A-(1-13)NH(2). Thus [NMePhe(1)]arodyn is a highly kappa opioid receptor-selective antagonist that could be a useful pharmacological tool to study kappa opioid receptor-mediated activities.</p>","PeriodicalId":22827,"journal":{"name":"The journal of peptide research : official journal of the American Peptide Society","volume":"65 3","pages":"322-32"},"PeriodicalIF":0.0,"publicationDate":"2005-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1399-3011.2005.00216.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25021176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detergent-assisted oxidative folding of delta-conotoxins.","authors":"R DeLa Cruz,&nbsp;F G Whitby,&nbsp;O Buczek,&nbsp;G Bulaj","doi":"10.1034/j.1399-3011.2003.00048.x","DOIUrl":"https://doi.org/10.1034/j.1399-3011.2003.00048.x","url":null,"abstract":"<p><p>Conotoxins comprise a diverse group of disulfide-rich peptides found in venoms of predatory Conus species. The native conformation of these peptides is marginally stable in comparison with alternative conformations, often resulting in low folding yields. The oxidative folding of hydrophobic delta-conotoxins was found to produce less than 1% of the native peptide [Bulaj, G. et al. (2001) Biochemistry 40, 13201]. In order to identify factors that might improve folding yields, we screened a number of additives including water-soluble polymers, detergents and osmolytes for their ability to increase steady-state accumulation of the native delta-conotoxin PVIA. The presence of a non-ionic detergent Tween and low temperature appeared to be the most effective factors in improving the oxidative folding. The detergent was also effective in promoting folding of other hydrophobic delta-conotoxins. Based on our findings, we discuss a possible mechanism for detergent-assisted folding and the general applicability of this mechanism to facilitating the proper folding of hydrophobic, cysteine-rich peptides.</p>","PeriodicalId":22827,"journal":{"name":"The journal of peptide research : official journal of the American Peptide Society","volume":"61 4","pages":"202-12"},"PeriodicalIF":0.0,"publicationDate":"2003-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1034/j.1399-3011.2003.00048.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22261374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amino acids with aryl-keto function in their side chains.","authors":"M A Bednarek","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Amino acids with aryl-keto function in their side-chains were obtained in excellent yields in the reaction of omega-carboxyamino acids with liquid HF in the presence of aromatic compounds susceptible to electrophilic substitution, such as anisole, 2-methoxybiphenyl, butyl phenyl ether or 1,3-dimethoxybenzene. The new amino acids were converted smoothly into N-tert-butyloxycarbonyl or N-fluorenylmethoxycarbonyl derivatives and then incorporated into peptides by conventional coupling methods. During the coupling step, no formation of cyclic Schiff bases was observed for aryl-keto amino acids derived from DL-alpha-aminopimelic acid and from L-alpha-aminosuberic acid. In the crude products, truncated peptides terminated at the keto amino acids were not detected by liquid chromatography-mass spectrometry.</p>","PeriodicalId":22827,"journal":{"name":"The journal of peptide research : official journal of the American Peptide Society","volume":"52 3","pages":"195-200"},"PeriodicalIF":0.0,"publicationDate":"1998-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20686113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inactivation and conformational changes of yeast invertase during unfolding in urea and guanidinium chloride solutions.","authors":"S Li,&nbsp;H P Yang,&nbsp;H M Zhou","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Yeast invertase exists in two different forms. The cytoplasmic enzyme is non-glycosylated, whereas the external invertase contains approximately 50% carbohydrate of the high mannose type. In this paper, the inactivation and the conformational changes of the yeast external invertase are analyzed for unfolding in urea and guanidinium chloride. The results show that much lower concentrations of denaturants are required to bring about inactivation than are required to produce significant conformational changes of the yeast external invertase. The results suggest that the active sites of the external invertase containing carbohydrate residues may display more conformational flexibility than the enzyme molecules as a whole.</p>","PeriodicalId":22827,"journal":{"name":"The journal of peptide research : official journal of the American Peptide Society","volume":"51 1","pages":"45-8"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20420856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insect neuropeptide proctolin and its analogues. An overview of the present literature.","authors":"D Konopińska","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In the present paper, the literature describing synthetic, biological and conformational studies on the insect neuropeptide proctolin (H-Arg-Tyr-Leu-Pro-Thr-OH) and its analogues is summarized. The paper covers proctolin and its 80 analogues modified in positions 1-5, a cycloanalogue and analogues with a truncated or elongated peptide chain. These peptides were bioassayed by different methods, e.g. studies of myotropic activities in several insect species in vitro and behaviour in rats in vivo. Based on these data structure-activity relationships are discussed.</p>","PeriodicalId":22827,"journal":{"name":"The journal of peptide research : official journal of the American Peptide Society","volume":"49 6","pages":"457-66"},"PeriodicalIF":0.0,"publicationDate":"1997-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20209862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of beta-turns.","authors":"K C Chou","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A residue-coupled model is proposed to predict the beta-turns in proteins. The rates of correct prediction for the 455 beta-turn tetrapeptides and 3807 non-beta-turn tetrapeptides in the training database are 94.7 and 81.3%, respectively. The rates of correct prediction for the 110 beta-turn tetrapeptides and 30,229 non-beta-turn tetrapeptides in the testing database are 80.0 and 80.2%, respectively. Compared with the rates of correct prediction based on the residue-independent model reported previously, the quality of prediction is significantly improved by the new model, implying that the residue-coupled effect along a polypeptide chain is important for the formation of reversal turns, such as beta-turns, during the process of protein folding.</p>","PeriodicalId":22827,"journal":{"name":"The journal of peptide research : official journal of the American Peptide Society","volume":"49 2","pages":"120-44"},"PeriodicalIF":0.0,"publicationDate":"1997-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20095140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crystal structures of heterochiral peptides. Part II. tert-Boc-valyl-D-alanyl-leucyl-alanyl methoxide.","authors":"V Nagarajan,&nbsp;V Pattabhi,&nbsp;A Johnson,&nbsp;V Bobde,&nbsp;S Durani","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Crystal structure of a heterochiral peptide, viz. Boc-Val1-D-Ala2-Leu3-Ala4-OMe with a D chiral residue in the second position of a sequence, has been determined [a = 40.44(1), b = 4.887(5), c = 15.381(5) A, beta = 109.6(1)degrees, space group C2, Z = 4, R = 0.11]. The peptide is in a parallel beta-sheet structure terminated by a distinct local bend. The structure is established by N-H...O as well as C alpha-H...O hydrogen bonds. The contiguous C alpha-H...O hydrogen bond observed in this structure is an unique observation.</p>","PeriodicalId":22827,"journal":{"name":"The journal of peptide research : official journal of the American Peptide Society","volume":"49 1","pages":"74-9"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20075897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin K-dependent carboxylase. In vitro inhibitory activity of cyclopentane and cyclohexane-derived analogues of glutamic acid and their conformational study by NMR and molecular dynamics in aqueous solution.","authors":"V Larue,&nbsp;J Gharbi-Benarous,&nbsp;F Acher,&nbsp;R Azerad,&nbsp;J P Girault","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The conformational analysis of four glutamic acid analogues containing a cyclopentyl or cyclohexyl ring, substituted in position 1 by a Boc-protected amino group and a methyl ester group and in position 3 by a free carboxylate group (6-9), has been carried out in an aqueous environment, by 1H and 13C NMR spectroscopy, and molecular dynamics (MD). These compounds have been shown to be weak competitive inhibitors (Ki approximately 20-65 mM) of the vitamin K-dependent carboxylation of Boc-Glu-OMe in rat liver microsomes independently of their ring size and stereochemical features. However, the cyclic trans isomers have been found more active than the cis ones, and Boc-trans-C5-OMe (9) is the most potent inhibitor in the series (cis and trans isomers are defined by the relative arrangement of the carboxyl functions). Such cyclic glutamyl derivatives may provide valuable informations on the preferred bioactive conformations of synthetic glutamyl substrates at the active site of the carboxylase. In aqueous solution, the Boc-cis- and trans-C6 esters exhibit chair conformations with exclusively equatorial and axial substituent positions, while the Boc-cis- and -trans-C5 compounds may display envelope E or 'twist' T conformations with the substituents in the following positions, equatorial; axial and isoclinal. For each compound, the conformations resulting from NMR and MD data were analyzed and classified according to the dihedral angles chi 1 and chi 2, the distances of functional groups, and the spatial charge distribution involving the free carboxyl group. A reduced number of conformational families were found to be in qualitative agreement with NMR and MD data. These results are discussed in relation with the carboxylase inhibitory activity of the analogues, and a spatial disposition of the glutamyl side chain that could be recognized by the carboxylase is deduced.</p>","PeriodicalId":22827,"journal":{"name":"The journal of peptide research : official journal of the American Peptide Society","volume":"49 1","pages":"28-45"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20076627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SPPS of difficult sequences. A comparison of chemical conditions, synthetic strategies and on-line monitoring.","authors":"M Dettin,&nbsp;S Pegoraro,&nbsp;P Rovero,&nbsp;S Bicciato,&nbsp;A Bagno,&nbsp;C Di Bello","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The H-Ala-Arg-(Ala)6-Lys-OH sequence is a biologically interesting 'difficult sequence' presenting N alpha-Fmoc deprotection and coupling problems. Different chemical conditions and synthetic strategies have been tested in order to overcome the problems due to sequence-dependent interactions. In particular, it was confirmed that different solvents in the deprotection step did not provide any significant improvement, but the use of a more efficient base in the deprotection mixture avoided insufficient unblocking of N alpha-protecting group; problems due to partial coupling in the last steps of the synthesis were solved by double coupling techniques. Moreover, the synthesis of the model peptide was carried out using both \"continuous flow' and \"batch' techniques. The present results demonstrate that on-line monitoring of the deprotection step by absorbance measurements represents a very effective tool to detect the onset of internal aggregations during the synthesis.</p>","PeriodicalId":22827,"journal":{"name":"The journal of peptide research : official journal of the American Peptide Society","volume":"49 1","pages":"103-11"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20075899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}