Jasmonic acid spraying does not induce tuberisation in short-day-requiring potato species kept in non-inducing conditions

The potato species Solanum andigena (Juz. and Buk.) and Solanum demissum (Lindl.) that both require short days for tuberisation were kept in either long days (16 h light), or short days (8 h light) with a 30-min night break mid-way through the dark period. Tuberisation of these species was inhibited under both conditions. Repeated spraying of these plants with up to 100 μM jasmonic acid did not induce them to tuberise even though jasmonic acid was shown to be taken up and transported within the plant. This result argues against jasmonic acid itself being the transported tuber-inducing signal, although it does not exclude a role for jasmonic acid later in tuber formation and development once induction has taken place.     

The effect of homocysteine thiolactone and its alpha methylated derivative on bone matrix in the mouse

Summary Homocysteine (HC) is a radiation protector but toxic to bone. Its derivative homocysteine thiolactone (HCTL) and the alpha-alkylated analogue (A-methyl-HCTL) was fed to mice for a period of six weeks in a daily dose of 50 mg/kg body weight. Parameters for bone matrix as collagen content, acid solubility of bone collagen, urinary bone collagen cross links (pyridinolines) and urinary acid glycosaminoglycans were determined. Urinary acid glycosaminoglycans were significantly reduced in the HCTL treated group but not in the alpha-methyl-homocysteine thiolactone (A-methyl-HCTL) group (controls: 45 ± 7 mg/mmol creatinine, homocysteine thiolactone 38 ± 5 mg/mmol creatinine, A-methyl HCTL 45 ± 6 mg/mmol creatinine).No differences were found for the parameters of bone collagen between the groups. The potent radiation protecting methylated derivative therefore did not change bone matrix and should be a candidate for further toxicological studies.     

The effect of ovariectomy on phenylalanine and tyrosine metabolism

Summary Although the regulatory activity of steroid hormones on amino acid metabolism has been described, no information is published on the effect of ovariectomy. We studied the influence of ovariectomy in Wistar rats determining the amino acids phenylalanine and tyrosine in liver, kidney, plasma and urine. 32 animals were used in the study, 12 animals were sham operated, 9 animals were ovariectomized and 11 rats were ovariectomized and supplemented with estradiol. No quantitative changes were detected comparing liver and kidney phenylalanine and tyrosine between the groups (sham operated rats liver phenylalanine 2,53nM/mg ± 1,07; liver tyrosine 1.95nM/mg ± 0.92; kidney phenylalanine 2.16nM/mg ± 0.53; kidney tyrosine 1.80nM/mg ± 0.39. Ovariectomized rats showed liver phenylalanine 3.07nM/mg ± 1.14; liver tyrosine 2.63nM/mg ± 1.01; kidney phenylalanine 2.30 nM/mg ± 0.74; kidney tyrosine 1.93nM/mg ± 0.63. Ovariectomized and estradiol supplemented rats presented with liver phenylalanine 2.84nM/mg ± 1.40; liver tyrosine 2.35nM/mg ± 1.28; kidney phenylalanine 1.91nM/mg ± 0.26, kidney tyrosine 1.67nM/mg ± 0.23.). When, however, the phenylalanine/tyrosine ratio in the liver was evaluated, ovariectomized rats showed a significant decrease of the quotient (p = 0.001). The phenylalanine/tyrosine ratio was restored by estradiol replacement. Our findings show that phenylalanine and tyrosine metabolism is under estradiol control. The effect on the metabolic changes could be mediated by enzyme systems as phenylalanine hydroxylase, tyrosine hydroxylase and tyrosine aminotransferase. Our results would be compatible with previous reports on the stimulatory effect of estradiol on these enzymes. The kidney phenylalanine/tyrosine ratio was unaffected by ovariectomy and/or estradiol replacement which can be easily explained by different pools, enzyme activities, filtration/reabsorption effects, etc.The urinary P/T ratio was decreased by ovariectomy and restored by estradiol replacement indicating endocrine control of renal reabsorption and secretion mechanisms.     

The structural features of effective antagonists of the luteinizing hormone releasing hormone

Summary The structure-activity data of 6 years on 395 analogs of the luteinizing hormone releasing hormone (LHRH) have been studied to determine effective substituents for the ten positions for maximal antiovulatory activity and minimal histamine release. The numbers of substituents studied in the ten positions are as follows: (41)¹-(12)²-(12)³-(5)⁴-(47)⁵-(52)⁶-(16)⁷-(18)⁸-(4)⁹-(8)¹⁰. In position 1, DNal and DQal were effective with the former being more frequently the better substituent. DpClPhe was uniquely effective in position 2. Positions 3 and 4 are very sensitive to change. D3Pal in position 3 and Ser in position 4 of LHRH were in the best antagonists. PicLys and cPzACAla were the most successful residues in position 5 with cPzACAla being the better substituent. Position 6 was the most flexible and many substituents were effective; particularly DPicLys. Leu⁷ was most often present in the best antagonists. In position 8, Arg was effective for both antiovulatory activity and histamine release; ILys was effective for potency and lesser histamine release. Pro⁹ of LHRH was retained. DAlaNH₂ ¹⁰ was in the best antagonists.Abbreviations AABLys N -(4-acetylaminobenzoyl)lysine - AALys N -anisinoyl-lysine - AAPhe 3-(4-acetylaminophenyl)lysine - Abu 2-aminobutyric acid - ACLys N -(6-aminocaproyl)lysine - ACyh 1-aminocyclohexanecarboxylic acid - ACyp 1-aminocyclopentanecarboxylic acid - Aile alloisoleucine - AnGlu 4-(4-methoxy-phenylcarbamoyl)-2-aminobutyric acid - 2ANic 2-aminonicotinic acid - 6ANic 6-aminonicotinic acid - APic 6-aminopicolinic acid - APh 4-aminobenzoic acid - APhe 4-aminophynylalanine - APz 3-amino-2-pyrazinecarboxylic acid - Aze azetidine-2-carboxylic acid - Bim 5-benzimidazolecarboxylic acid - BzLys N -benzoyllysine - Cit citrulline - Cl₂Phe 3-(3,4-dichlorphenyl)alanine - cPzACAla cis-3-(4-pyrazinylcarbonylaminocyclohexyl)alnine - cPmACAla cis-3-[4-(4-pyrimidylcarbonyl)aminocyclohexyl]alanine - Dbf 3-(2-dibenzofuranyl)alanine - DMGLys N -(N,N-dimethylglycyl)lysine - Dpo N -(4,6-dimethyl-2-pyrimidyl)-ornithine - F₂Ala 3,3-difluoroalanine - hNal 4-(2-naphthyl)-2-aminobutyric acid - HOBLys N -(4-hydroxybenzoyl)lysine - hpClPhe 4-(4-chlorophenyl)-2-amino-butyric acid - Hse homoserine, 2-amino-4-hydroxybutanoic acid - ICapLys N -(6-isopropylaminocaproyl)lysine - ILys N -isopropyllysine - Ind indoline-2-carboxylic acid - INicLys N -isonicotinoyllysine - IOrn N -isopropylornithine - Me₃Arg N^G,N^G,N^G-trimethylarginine - Me₂Lys N ,N -dimethyllysine - MNal 3-[(6-methyl)-2-naphtyl]alanine - MNicLys N -(6-methylpicolinoyl)lysine - MPicLys N -(6-methylpicolinoyl)lysine - MOB 4-methoxybenzoyl - MpClPhe N-methyl-3-(4-chlorphenyl)lysine - MPZGlu glutamic acid,-4-methylpiperazine - Nal 3-(2-naphthyl)alanine - Nap 2-naphthoic acid - NicLys N -nicotinoyllysine - NO₂B 4-nitrobenzoyl - NO₂Phe 3-(4-nitrophenyl)alanine - oClPhe 3-(2-chlorphenyl)alanine - Opt O-phenyl-tyrosine - Pal 3-(3-pyridyl)alanine - 2Pal 3-(2-pyridyl)alanine - 2PALys N -(3-pyridylacetyl)lysine - pCapLys N -(6-picolinoylaminocaproyl)lysine - pClPhe 3-(4-chlorophenyl)alanine - pFPhe 3-(4-fluorophenyl)-alanine - Pic picolinic acid - PicLys N -picolinoyllysine - Pip piperidine-2-car-boxylic acid - PmcLys N -(4-pyrimidylcarbonyl)lysine - Ptf 3-(4-trifluromethyl phenyl)alanine - Pz pyrazinecarboxylic acid - PzAla 3-pyrazinylalanine - PzAPhe 3-(4-pyrazinylcarbonylaminophenyl)alanine - Qal 3-(3-quinolyl)alanine - Qnd-Lys N -quinaldoyllysine - Qui 3-quinolinecarboxylic acid - Qux 2-quinoxalinecarboxylic acid - Tic 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid - TinGly 2-thienylglycine - tNACAla trans-3-(4-nicotinoylaminocyclohexyl)-alanine - tPACAla trans-3-(4-picolinoylaminocyclohexyl)alanine     

Chirospecific synthesis of D and Lp-chlorohomophenylalanine N-t-BOC DCHA salts

Summary The chirospecific conversions of D-glucosamine hydrochloride and D-mannosamine hydrochloride to the configurationally stable L and D isomers of N-t-butyloxycarbonylserinal were carried out byt-butylcarbonylation followed by sodium borohydride reduction and sodium meta-periodate oxidation. Reaction of the L and D aldehydes with the Wittig reagent prepared from 4-chlorobenzyltriphenylphosphonium chloride and butyl lithium followed by catalytic hydrogenation, Jones oxidation and salt formation with dicyclohexylamine gave the DCHA salts of the D and L isomers ofp-chlorohomophenylalanine N-t-Boc in high enatiomeric excess. The optical purity of the title compounds was established by hydrolysis to the respective free amino acids, followed by chiral derivatization and HPLC analysis.This was presented at the Fifth International Kyoto Conference on new Aspects of Organic Chemistry, Kyoto, Japan, November 11–15, 1991. Abstract #GO-13.     

Lipophilicity of amino acids

Summary The lipophilicity (or hydrophobicity) of amino acids is an important property relevant for protein folding and therefore of great interest in protein engineering. For peptides or peptidomimetics of potential therapeutic interest, lipophilicity is related to absorption and distribution, and thus indirectly relates to their bioactivity. A rationalization of peptide lipophilicity requires basic knowledge of the lipophilicity of the constituting amino acids. In the present contribution we will review methods to measure or calculate the lipophilicities of amino acids, including unusual amino acids, and we will make a comparison between various lipophilicity scales.     

Effect of arachidonic acid on [3H]d-aspartate outflow in the rat hippocampus

The aim of this study was to investigate the effect of arachidonic acid on [³H]d-aspartate outflow in rat hippocampus synaptosomes and slices. Arachidonic acid 1) increased basal outflow of [³H]d-aspartate in both synaptosomes and slices, and 2) increased K⁺-evoked overflow in slices but not in synaptosomes. The latter effect was dependent (at least in part) on arachidonic acid metabolism, most likely mediated by lipo-oxygenase metabolites and free radical production. It was prevented by nordihydroguaiaretic acid but not by indomethacin, and was significantly reduced by free radical scavengers (superoxide-desmutase and catalase). This effect was dependent upon stimulation since it could not be observed after a continuous perfusion of arachidonic acid in the absence of stimulation. Furthermore, it was long-lasting since a 30 min perfusion of arachidonic acid was sufficient to exert a significant effect on a stimulation following termination of the application.     

Chiral copper(I)—thiolate clusters in metallothionein and glutathione

Metallothionein (MT) is a ubiquitous mammalian protein comprising 61 or 62 nonaromatic amino acids of which 20 are cysteine residues. The high sulfhydryl content imparts to this protein a unique and remarkable ability to bind multiple metal ions in structurally significant metal–thiolate clusters. MT can bind seven divalent metal ions per protein molecule in two domains with exclusive tetrahedral metal coordination. The domain stoichiometries for the M₇S₂₀ structure are M₄(S_cys)₁₁ (α domain) and M₃(S_cys)₉ (β domain). Up to 12 Cu(I) ions can displace the 7 Zn²⁺ ions bound per molecule in Zn₇–MT. The incoming Cu(I) ions adopt a trigonal planar geometry with domain stoichiometries for the Cu₁₂S₂₀ structure of Cu₆(S_cys)₁₁ and Cu₆(S_cys)₉ for the α and β domains, respectively. The circular dichroism (CD) spectra recorded as Cu⁺ is added to Zn₇–MT to form Cu₁₂–MT directly report structural changes that take place in the metal binding region. The spectrum arises under charge transfer transitions between the cysteine S and the Cu(I); because the Cu(I)–thiolate cluster units are located within the chiral binding site, intensities in the CD spectrum are directly related to changes in the binding site. The CD technique clearly indicates stoichiometries of several Cu(I)–MT species. Model Cu(I)–thiolate complexes, using the tripeptide glutathione as the sulfhydryl source, were examined by CD spectroscopy to obtain transition energies and the Cu(I)–thiolate coordination geometries which correspond to these bands. Possible structures for the Cu(I)–thiolate clusters in the α and β domains of Cu₁₂–MT are proposed. © 1994 Wiley-Liss, Inc.     

Salicylic acid inhibits the biosynthesis of ethylene in detached rice leaves

The effects of salicylic acid (SA) on ethylene biosynthesis in detached rice leaves were investigated. SA at pH 3.5 effectively inhibited ethylene production within 2 h of its application. It inhibited the conversion of ACC to ethylene, but did not affect the levels of ACC and conjugated ACC. Thus, the inhibitory effect of SA resulted from the inhibition of both synthesis of ACC and the conversion of ACC to ethylene.Abbreviations ACC 1-aminocyclopropane-1-carboxylic acid - EFE ethylene-forming enzyme - SA salicylic acid     

Peroxisome proliferators as inducers and substrates of UDP-glucuronosyltransferases

Summary— Peroxisome proliferators, despite their chemically unrelated structures, share the common property of being able to stimulate the glucuronidation of bilirubin in rodents and, probably, also in man. The aryloxycarboxylic acids (clofibric acid, fenofibrate, bezafibrate, ciprofibrate), tiadenol and probucol, all of which have hypolipidemic properties, as well as the fatty acid-like perfluorodecanoic acid all enhanced the expression of the UDP-glucuronosyltransferase (UGT) form involved in the conjugation of the pigment. This induction is manifested by an increase in the mRNA species encoding the protein with a subsequent increase in the neosynthesis of the corresponding protein in the endoplasmic reticulum. The induction process is concomitant with that of cytochrome P-450-IVA1 and cytosolic epoxide hydrolase, which, like bilirubin UGT, are mainly involved in the metabolism of endogenous substrates. With a series of carboxylic acids related to clofibric acid, it was possible to demonstrate that induction was mediated via specific interactions based on the physicochemical properties of the inducers. Until now, the molecular basis of induction of bilirubin UGT is not known. The peroxisome proliferators that possess a carboxyl group are good substrates of UGT, especially in man. The acylglucuronides formed are known for their instability and reactivity which could contribute to the toxicity encountered in some patients treated with the drugs. There is convincing evidence that UGT bilirubin does not catalyze the glucuronidation of these substances even if the two types of substrate form acylglucuronides.