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1.
(+)-2,9 alpha-Dimethyl-5-(m-hydroxyphenyl)morphan is the only phenylmorphan analog whose affinity for opioid kappa-receptors is greater than its affinity for opioid mu-receptors. Pharmacologically, the compound is a pure opioid antagonist devoid of agonist activity in in vivo assays of antinociception. The absolute configuration of the compound has been determined to be (1R,5S,9R) from an X-ray crystallographic study of the chloride salt. Thus, the absolute configuration corresponds to that of the atypical opioid agonist (-)-phenylmorphan while the weak atypical agonist (-)-2,9 alpha-dimethyl-5-(m- hydroxyphenyl)morphan corresponds to the potent morphine-like (+)-phenylmorphan. The preferred orientations of the phenyl ring for the two stereoisomers were determined using the molecular mechanics program MM2-87 and found to vary from that of the two parent compounds. The atypical properties of the two 9 alpha-methyl analogs is consistent with an opioid ligand model which proposes that morphine-like properties require a particular range of phenyl orientations. There was good agreement between the structure obtained from X-ray crystallography and computed with the MM2-87 program. 相似文献
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Kalaiyarasi Ramalingam Scott R. Eaton Wayne L. Cody Joseph A. Loo Annette M. Doherty 《Letters in Peptide Science》1994,1(2):73-79
Summary A series of phosphopeptides Tyr(PO3H2)-Val-Pro-Xxx-Leu (Xxx=Met, Met(O), Nle, Dab or Cys), derived from the native platelet-derived growth factor- receptor (PDGF-) sequence, has been prepared to study their interaction with the src-homology 2 (SH2) domains of the p85 subunit of PI3 kinase. The phosphopeptides were synthesized using Fmoc methodology incorporating N-Boc dibenzyl-protected phosphotyrosine (Boc-Tyr[PO3(Bzl)2]) as the N-terminal amino acid, since the benzyl groups can be removed during resin cleavage with TFA. Only peptides containing methionine were found to exist partially as S-benzyl sulfonium salts after TFA cleavage from the resin. The desired peptide could be obtained from the S-benzyl sulfonium salt by hydrogenolysis. 相似文献
4.
Cody Raul Cardenas Andrew J. Mularo Andreas S. Chavez Rachelle M. M. Adams 《Biotropica》2023,55(1):145-159
The coevolutionary relationship between fungus-growing ants (Formicidae: Attini: Attina) and their symbionts has been well studied in the Panamanian rain forests. To further understand the ecological context of these evolutionary relationships, we have examined the population-genetic structure of the fungus-growing ant species Mycetomoellerius mikromelanos Cardenas, Schultz, Adams 2021 in the Panama Canal Zone. We specifically investigated the presence of population structure, the significance of geographic features (i.e., creeks) limiting gene flow, and relatedness between ant colonies. To accomplish this, we genotyped 85 ant colonies from nine creeks across an approximately 30 km transect in Parque National Soberanía, Panama, using double-digest restriction-site-associated DNA sequencing. We did not find distinct population structure using two genetic clustering methods; however, we did detect an effect of isolation by distance. Furthermore, related colonies were frequently detected on the same creek or neighboring creeks, and some at further geographic distances. Collectively, these findings demonstrate that new colonies tend to establish on natal creeks and occasionally on distant creeks following long-distance dispersal events. We discuss how population-genetic patterns reveal the natural history of M. mikromelanos in Parque National Soberanía and how these results fit into the context of fungus-growing ant mutualisms. Abstract in Spanish is available with online material. 相似文献
5.
M D Hirsch T L O'Donohue R Wilson T K Sawyer V J Hruby M E Hadley W L Cody J J Knittel J N Crawley 《Peptides》1984,5(6):1197-1201
Previous studies have identified the (4-10) heptapeptide sequence as the central core of alpha-MSH/ACTH peptides required for mediation of important biological activities. In the present study, the structure-activity relationships of Nle4-substituted and Cys4,Cys10-bridged cyclic alpha-MSH analogues, which were previously shown to exhibit a wide range of melanotropic potencies from weak agonism to super potency, were examined for grooming behavioral activity in the rat following intracerebroventricular injections. The results showed that stepwise C-terminal elongation of the linear Nle4-substituted Ac-alpha-MSH4-10-NH2 increased grooming potencies of the peptides in a manner similar to their actions on melanocytes. The most interesting finding was the observation that cyclization of the inactive linear "central (4-10) core" of alpha-MSH (Ac-alpha-MSH4-10) to form Ac-[Cys4,Cys10]-alpha-MSH4-10-NH2 resulted in a super potent agonist in the grooming assay. However, while cyclization of the (4-10) heptapeptide produced potent agonists on grooming behavior, the structure-activity relationships were different than the frog skin bioassay. These findings support the hypothesis that appropriate structural and confirmational modifications of alpha-MSH-related peptides can produce profound effects on the bioactivities of the peptides, and suggest that different structural-conformational requirements exist for alpha-MSH interactions with its various receptors. 相似文献
6.
Defective lysis of streptomycin-resistant escherichia coli cells infected with bacteriophage f2 总被引:2,自引:1,他引:1
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A lysis defect was found to account for the failure of a streptomycin-resistant strain of Escherichia coli to form plaques when infected with the male-specific bacteriophage f2. The lysis defect was associated with the mutation to streptomycin resistance. Large amounts of apparently normal bacteriophage accumulated in these cells. Cell-free extracts from both the parental and mutant strains synthesized a potential lysis protein in considerable amounts in response to formaldehyde-treated f2 RNA but not in response to untreated RNA. As predicted from the nucleotide sequence of the analogous MS2 phage, the protein synthesized in vitro had the expected molecular weight and lacked glycine. The cistron for the lysis protein overlapped portions of the coat and replicase cistrons and was translated in the +1 reading frame. Initiation at the lysis protein cistron may be favored by translation errors that expose the normally masked initiation site, and streptomycin-resistant ribosomes, known to have more faithful translation properties, may be unable to efficiently synthesize the lysis protein. 相似文献
7.
The crystal and molecular structure of the fluorescent probe 8-anilino-1-naphthalenesulfonic acid (ANS) has been determined as the ammonium monohydrate with two conformationally distinct molecules in the triclinic lattice. The angles between the aromatic rings and the CNC plane are ?9/22° and 112/22° respectively. There is an NH...O intramolecular hydrogen bond in each molecule indicating that hydrogen bond formation is not dependent on the anilino geometry. There are also short intramolecular H...H contacts involving the hydrogens which have anomalous proton shifts shown in a recent NMR study. 相似文献
8.
Dana J Sowa Monica M Warner Andriana Tetenych Lucas Koechlin Pardis Balari Jose
Pablo Rascon
Perez Cody Caba Sara N Andres 《Nucleic acids research》2022,50(19):11040
Bacterial non-homologous end joining requires the ligase, LigD and Ku. Ku finds the break site, recruits LigD, and then assists LigD to seal the phosphodiester backbone. Bacterial Ku contains a core domain conserved with eukaryotes but has a unique C-terminus that can be divided into a minimal C-terminal region that is conserved and an extended C-terminal region that varies in sequence and length between species. Here, we examine the role of Mycobacterium tuberculosis Ku C-terminal variants, where we removed either the extended or entire C-terminus to investigate the effects on Ku–DNA binding, rates of Ku-stimulated ligation, and binding affinity of a direct Ku–LigD interaction. We find that the extended C-terminus limits DNA binding and identify key amino acids that contribute to this effect through alanine-scanning mutagenesis. The minimal C-terminus is sufficient to stimulate ligation of double-stranded DNA, but the Ku core domain also contributes to stimulating ligation. We further show that wildtype Ku and the Ku core domain alone directly bind both ligase and polymerase domains of LigD. Our results suggest that Ku-stimulated ligation involves direct interactions between the Ku core domain and the LigD ligase domain, in addition to the extended Ku C-terminus and the LigD polymerase domain. 相似文献
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10.
Genetic architecture,biochemical underpinnings and ecological impact of floral UV patterning
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Marcus T. Brock Lauren K. Lucas Nickolas A. Anderson Matthew J. Rubin R. J. Cody Markelz Michael F. Covington Upendra K. Devisetty Clint Chapple Julin N. Maloof Cynthia Weinig 《Molecular ecology》2016,25(5):1122-1140
Floral attraction traits can significantly affect pollinator visitation patterns, but adaptive evolution of these traits may be constrained by correlations with other traits. In some cases, molecular pathways contributing to floral attraction are well characterized, offering the opportunity to explore loci potentially underlying variation among individuals. Here, we quantify the range of variation in floral UV patterning (i.e. UV ‘bulls‐eye nectar guides) among crop and wild accessions of Brassica rapa. We then use experimental crosses to examine the genetic architecture, candidate loci and biochemical underpinnings of this patterning as well as phenotypic manipulations to test the ecological impact. We find qualitative variation in UV patterning between wild (commonly lacking UV patterns) and crop (commonly exhibiting UV patterns) accessions. Similar to the majority of crops, recombinant inbred lines (RILs) derived from an oilseed crop × WI fast‐plant® cross exhibit UV patterns, the size of which varies extensively among genotypes. In RILs, we further observe strong statistical‐genetic and QTL correlations within petal morphological traits and within measurements of petal UV patterning; however, correlations between morphology and UV patterning are weak or nonsignificant, suggesting that UV patterning is regulated and may evolve independently of overall petal size. HPLC analyses reveal a high concentration of sinapoyl glucose in UV‐absorbing petal regions, which, in concert with physical locations of UV‐trait QTLs, suggest a regulatory and structural gene as candidates underlying observed quantitative variation. Finally, insects prefer flowers with UV bulls‐eye patterns over those that lack patterns, validating the importance of UV patterning in pollen‐limited populations of B. rapa. 相似文献