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821.
Abstract. Antennal movement responses of male Glossina morsitans morsitans Westwood to twelve analogues of the tsetse olfactory attractant 1-octen-3-ol were investigated to determine their structure-activity relationships. The results indicate that the chemoreceptors which perceive this set of kairomones may not be highly specific. Activity is dependent on the length of the alkyl chain; also homologues with odd alkyl chains such as 3-buten-2-ol, 1-hexen-3-ol and 1-octen-3-ol evoked higher antennal responses than homologues with even alkyl chains such as l-nonen-3-ol, 1-hepten-3-ol and 1-penten-3-ol. Comparison of the activities of eight carbon structural variants of 1-octen-3-ol showed that the structural requirements for activity of the functional end of the molecule may not be rigid; thus, 1-octyn-3-ol elicited relatively high responses. However, low responses to 1-octene and 3-octanol showed that both the π electron system as well as the oxygen function are important for activity. Laboratory bioassay findings indicate that compounds such as 1-octyn-3-ol, 3-buten-2-ol, allyl alcohol and 1-octen-3-one which evoke antennal responses 2–3 times greater than the control have attractive properties and preliminary field investigations show that 3-buten-2-ol and allyl alcohol significantly increase trap catches. 相似文献
822.
Efthimia Theodoropoulou Thomas Mavromoustakos Dimitris Panagiotopoulos John M. Matsoukas Julian Smith 《Letters in Peptide Science》1996,3(4):209-216
Summary The model of angiotensin II (ANG II) developed in our laboratory using a combination of NMR, fluorescence data and molecular graphics [Matsoukas, J.M. et al., J. Biol. Chem., 269 (1994) 5303] served as a template for a systematic superimposition of potent AT1 receptor antagonists with ANG II. The key amino acids in this model, tyrosine, phenylalanine and histidine, form a charge-relay system. The studied ANG II AT1 receptor antagonists were found to accommodate this relay system. The proposed model offers a motivation to synthetic chemists to develop ANG II antagonists that differ from the losartan prototype structure but possess an enhanced biological profile. 相似文献
823.
Summary By analogy to established methodology for the preparation of C-terminal peptide amides by 9-fluorenylmethyl-oxycarbonyl (Fmoc) chemistry, in conjunction with the acidolyzable 5-(4-Fmoc-aminomethyl-3,5-dimethoxyphenoxy)valeric acid (PAL, 1) handle, the present paper reports on 5-(4-(N-Fmoc-N-alkyl)aminomethyl-3,5-dimethoxyphenoxy)valeric acid [(R)PAL, 2] handles that can be used for synthesis of peptide N-alkylamides. The key step in the preparation of these handles was the NaBH3CN-mediated reductive amination (60 to 85% yields; R=CH3, CH3CH2, C6H5CH2CH2, 4-NO2C6H5) of 5-(4-formyl-3,5-dimethoxyphenoxy)valeric acid (4), an aldehyde precursor to PAL. The (R)PAL handles (2a and b) were applied to the preparation of LHRH analogues. After anchoring of handles to PEG-PS supports, peptide chain assemblies were carried out, and treatments with TFA-thioanisolephenol-1,2-ethanedithiol (87:5:5:3) for 90 min at 25 °C, followed by aqueous workups, provided the expected products in excellent yields and purities as supported by HPLC and mass spectrometric characterization.Taken in part from the Ph.D. Thesis of M.F. Songster, University of Minnesota, 1996. Preliminary reports of this work were presented at the 14th American Peptide Symposium, Columbus, OH, June 18–23, 1995 (poster P047), and at the Fourth International Symposium on Solid Phase Synthesis and Combinatorial Chemical Libraries, Edinburgh, Scotland, UK, September 12–16, 1995. 相似文献
824.
Marcel Hollenstein Christine Catherine Smith Michael R?z 《Journal of visualized experiments : JoVE》2014,(86)
The traditional strategy for the introduction of chemical functionalities is the use of solid-phase synthesis by appending suitably modified phosphoramidite precursors to the nascent chain. However, the conditions used during the synthesis and the restriction to rather short sequences hamper the applicability of this methodology. On the other hand, modified nucleoside triphosphates are activated building blocks that have been employed for the mild introduction of numerous functional groups into nucleic acids, a strategy that paves the way for the use of modified nucleic acids in a wide-ranging palette of practical applications such as functional tagging and generation of ribozymes and DNAzymes. One of the major challenges resides in the intricacy of the methodology leading to the isolation and characterization of these nucleoside analogues.In this video article, we present a detailed protocol for the synthesis of these modified analogues using phosphorous(III)-based reagents. In addition, the procedure for their biochemical characterization is divulged, with a special emphasis on primer extension reactions and TdT tailing polymerization. This detailed protocol will be of use for the crafting of modified dNTPs and their further use in chemical biology. 相似文献
825.
Wei-Chih Chao Li-Ju Lin Jyh-Feng Lu Jinn-Shyan Wang Tzu-Chieh Lin Yi-Han Chen Yi-Ting Chen Hsiao-Ching Yang Pi-Tai Chou 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(3):451-459
We carried out comprehensive spectroscopic studies of wild type and mutants of ascorbate peroxidase (APX) to gain understanding of the conformational mobility of the active site. In this approach, three unnatural tryptophans were applied to replace the distal tryptophan (W41) in an aim to probe polarity/water environment near the edge of the heme-containing active site. 7-azatryptophan ((7-aza)Trp) is sensitive to environment polarity, while 2,7-azatryptophan ((2,7-aza)Trp) and 2,6-diazatryptophan ((2,6-aza)Trp) undergo excited-state water-catalyzed double and triple proton transfer, respectively, and are sensitive to the water network. The combination of their absorption, emission bands and the associated relaxation dynamics of these fluorescence probes, together with the Soret-band difference absorption and resonance Raman spectroscopy, lead us to unveil the water associated conformational mobility in the active site of APX. The results are suggestive of the existence of equilibrium between two different environments surrounding W41 in APX, i.e., the water-rich and water-scant forms with distinct fluorescence relaxation. Our results thus demonstrate for the first time the power of integrating multiple sensors (7-aza)Trp, (2,7-aza)Trp and (2,6-aza)Trp in probing the water environment of a specifically targeted Trp in proteins. 相似文献
826.
S. G. Romanova A. A. Shtil’ G. A. Serebrennikova 《Russian Journal of Bioorganic Chemistry》2008,34(6):743-746
Modified series of phosphorusless edelfosine analogues bearing the polar heads of aliphatic bases, N,N-dimethylethanolamine and N,N,N1,N1-tetramethylethylenediamine, were synthesized, with the length of the spacer varying from three to four methylene units. The cytotoxic characteristics of the compounds synthesized were studied. 相似文献
827.
Inhibition of [3 H]GABA Binding to Postsynaptic Receptors in Human Cerebellar Synaptic Membranes by Carboxyl and Amino Derivatives of GABA 总被引:2,自引:0,他引:2
Robin J. Breckenridge Sydney H. Nicholson Alan J. Nicol Colin J. Suckling Beatrice Leigh Leslie Iversen 《Journal of neurochemistry》1981,37(4):837-844
Fifty synthetic analogues of GABA were tested for their ability ot interact with GABA receptors, using [3H]GABA binding to human cerebellar membranes as an in vitro model. The most active compounds were found to be aliphatic and heterocyclic aminosulphonic acids. Compounds with highly substituted nitrogen atoms were only weakly active unless a long alkyl chain, which can interact with the postsynaptic membrane, was present. It was concluded that a pyramidal nitrogen atom is favoured fro binding of GABA analogues to human cerebellar membranes. 相似文献
828.
Giovanna Pirri Andrea Giuliani Silvia Fabiole Nicoletto Lorena Pizzuto Andrea C. Rinaldi 《Central European Journal of Biology》2009,4(3):258-273
Lipopeptide antibiotics represent an old class of antibiotics that were discovered over 50 years ago, which includes the old
polymyxins but also new entries, such as the recently approved daptomycin. They generally consist of a hydrophilic cyclic
peptide portion attached to a fatty acid chain which facilitates insertion into the lipid bilayer of bacterial membranes.
This review presents an overview of this class of antibiotics, focusing on their therapeutic applications and putting particular
emphasis on chemical modifications introduced to improve their activity. 相似文献
829.
《Bioorganic & medicinal chemistry》2020,28(3):115260
Mitoxantrone is an anticancer anthracenedione that can be activated by formaldehyde to generate covalent drug-DNA adducts. Despite their covalent nature, these DNA lesions are relatively labile. It was recently established that analogues of mitoxantrone featuring extended side-chains terminating in primary amino groups typically yielded high levels of stable DNA adducts following their activation by formaldehyde. In this study we describe the DNA sequence-specific binding properties of the mitoxantrone analogue WEHI-150 which is the first anthracenedione to form apparent DNA crosslinks mediated by formaldehyde. The utility of this compound lies in the versatility of the covalent binding modes displayed. Unlike other anthracenediones described to date, WEHI-150 can mediate covalent adducts that are independent of interactions with the N-2 of guanine and is capable of adduct formation at novel DNA sequences. Moreover, these covalent adducts incorporate more than one formaldehyde-mediated bond with DNA, thus facilitating the formation of highly lethal DNA crosslinks. The versatility of binding observed is anticipated to allow the next generation of anthracenediones to interact with a broader spectrum of nucleic acid species than previously demonstrated by the parent compounds, thus allowing for more diverse biological activities. 相似文献
830.
《Bioorganic & medicinal chemistry》2016,24(16):3396-3405
The serine–threonine protein kinase Akt, also known as protein kinase B, is a key component of the phosphoinositide 3-kinase (PI3K)–Akt–mTOR axis. Deregulated activation of this pathway is frequent in human tumors and Akt-dependent signaling appears to be critical in cell survival. PI3K activation generates 3-phosphorylated phosphatidylinositols that bind Akt pleckstrin homology (PH) domain. The blockage of Akt PH domain/phosphoinositides interaction represents a promising approach to interfere with the oncogenic potential of over-activated Akt. In the present study, phosphatidyl inositol mimics based on a β-glucoside scaffold have been synthesized as Akt inhibitors. The compounds possessed one or two lipophilic moieties of different length at the anomeric position of glucose, and an acidic or basic group at C-6. Docking studies, ELISA Akt inhibition assays, and cellular assays on different cell models highlighted 1-O-octadecanoyl-2-O-β-d-sulfoquinovopyranosyl-sn-glycerol as the best Akt inhibitor among the synthesized compounds, which could be considered as a lead for further optimization in the design of Akt inhibitors. 相似文献