Metabolites of the pathogenic fungusVerticillium dahliae. XI. Primary structure of the polypeptide moiety of the phytotoxic pigment PKZh-1

The sequence of the 27 amino acid residues composing the polypeptide moiety of the phytotoxic metabolite PKZh-1 of the fungusV. dahliae has been determined on the basis of the structures of tryptic and chymotryptic peptides. It has been established that the linkage of the polypeptide with 2,5,7-trihydroxy-1,4-naphthoquinone (flaviolin), which is the chromophoric moiety of PKZh-1, is effected through an ester bond formed by the carboxy group of the C-terminal amino acid and one of the hydroxy groups of flaviolin.Deceased.V. I. Lenin Tashkent State University. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 630–636, September–October, 1981.     

Metabolites of the pathogenic fungus Verticillium dahliae VII. The phytotoxic pigment PKZh-1 from the culture liquid

Summary The phytotoxic pigment PKZh-1 that causes the characteristic symptoms of wilt in tests on cotton-plant shoots in a concentration of 100–150 µg/ml, has been isolated from the culture liquid of the fungusVerticillium dahliae Kleb.On the basis of qualitative reaction, spectral characteristics, and a study of hydrolysis products, PKZh-1 has been assigned to the peptide group. A red substance identified as 3,6,8-trihydroxy-1,4-naphthaquinone has been isolated from an acid hydrolyzate of PKZh-1.V. I. Lenin Tashkent State University. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 690–693, September–October, 1977.     

Metabolites of the pathogenic fungusVerticillium dahliae VIII. Interaction of the phytotoxic metabolite PKZh-1 with Na+,K+-ATPase

Summary It has been established that the phototoxic metabolite PKZh-1 of the fungusV. dahliae and, to a smaller extent, its chromophoric moiety possess an inhibiting action on the Na⁺,K⁺-ATPase of the microsomal fraction of the cells of the root hairs of the cotton plant of variety 108-F.The absence of specificity in the action of the phytotoxin has been shown in experiments on the Na⁺,K⁺-ATPase of the microsomal fractions of the cells of the cerebral cortexes of the ox, rat, and frog, bovine kidney, and tarantula ganglion.V. I. Lenin Tashkent State University. Institute of Biochemistry of the Academy of Sciences of the Uzbek SSR, Tashkent. Translated from Khimiya Prirodnykh Soedinenii, No. 1, pp. 59–62, January–February, 1979.     

Polysaccharides of brown algae

Conclusions A sulfated peptidoglycuronoglycan, pelvecyan, has been isolated from the brown algaP. wrightii. Its carbohydrate moiety contains D-galactose, D-mannose, D-xylose, L-fucose, and hexuronic acid residues. The polypeptide component consists of 16 amino acids and may be bound to the polysaccharide moiety by ionic bonds.Pelvecyan is similar in nature and properties to sargassan, which was isolated from the brown algaSargassum pallidum.Khimiya Prirodnykh Soedinenii, Vol. 6, No. 4, pp. 400–402, 1970     

Molecular assembly of Zn porphyrin complexes onto a gold electrode using synthetic light-harvesting model polypeptides

Molecular assembly of Zn porphyrin pigments, Zn substituted bacteriochlorophyll a ([Zn]-BChl a) and Zn mesoporphyrin monomer (ZnMPMME) on a gold electrode using synthetic 1α-helix hydrophobic polypeptides which have similar amino acid sequences to the hydrophobic core in the native photosynthetic light-harvesting (LH) 1-β polypeptide from Rhodobacter sphaeroides, has been achieved: this process is dependent on the structures of pigments and polypeptides. Interestingly, an enhanced photoelectric current was observed when ZnMPMME with the LH1 model polypeptide in an α-helical configuration was assembled onto the electrode.     

Metabolites of the pathogenic fungus Verticillium dahliae VI. Pentaketide metabolites and neutral lipids of virulent and avirulent strains

Summary A comparative study of the amounts of the phytotoxic pigment PKZh-1 and of extracellular and intracellular lipids in five strains and mutants ofVerticillium dahliae differing in virulence and in the nonpathogenic fungusV. lateritium has been made. A definite correlation has been found between virulence and PKZh-1 content.It has been established that the extracellular lipids are produced in considerable amounts by the virulent strains while in the avirulent mutants and inV. lateritium they are absent or present in only very small amount. The contents of neutral lipids in the mycelia of strains and mutants differing in virulence do not differ significantly. There are definite differences in the compositions of the neutral lipids and in the fatty-acid compositions of the individual classes of lipids.From the culture liquid of one of the avirulent strains (R-196), 3,6,8-trihydroxy-1,2,3,4-tetrahydronaphthalen-1-one has been isolated.V. I. Lenin State University. Institute of the Chemistry of Plant Substances, Academy of Sciences of the Uzbek SSR, Tashkent. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 632–635, September–October, 1977.     

<em>In Vitro</em> Anti-diabetic Activities and Chemical Analysis of Polypeptide-k and Oil Isolated from Seeds of <em>Momordica charantia</em> (Bitter Gourd)

The amino acid and fatty acid composition of polypeptide k and oil isolated from the seeds of Momordica charantia was analysed. The analysis revealed polypeptide k contained 9 out of 11 essential amino acids, among a total of 18 types of amino acids. Glutamic acid, aspartic acid, arginine and glycine were the most abundant (17.08%, 9.71%, 9.50% and 8.90% of total amino acids, respectively). Fatty acid analysis showed unusually high amounts of C18-0 (stearic acid, 62.31% of total fatty acid). C18-1 (oleic acid) and C18-2 (linoleic acid) were the other major fatty acid detected (12.53% and 10.40%, respectively). The oil was devoid of the short fatty acids (C4-0 to C8-0). Polypeptide k and oil were also subjected to in vitro α-glucosidase and α-amylase inhibition assays. Both polypeptide k and seed oil showed potent inhibition of α-glucosidase enzyme (79.18% and 53.55% inhibition, respectively). α-Amylase was inhibited by 35.58% and 38.02%, respectively. Collectively, the in vitro assay strongly suggests that both polypeptide k and seed oil from Momordica charantia are potent potential hypoglycemic agents.     

Structure of the peptide moiety of verticillin

The amino acid sequence of the peptide moiety of verticillin (I) - a phytotoxic metabolite of the causative agent of verticillium wilt of the cotton plant - has been determined. On the basis of the determination of the amino acid sequences of five short peptides isolated from the products of incomplete acid hydrolysis of oxidized desferriverticillin, the structure cyclo[L-glycyl-L-seryl-L-glycyl(L--N-hydroxyornithyl)] has been established for the peptide moiety of (I).     

Hydroxynorleucine as a glycosyl acceptor is an efficient means for introducing amino acid functionality into complex carbohydrates

A new approach to the synthesis of biologically relevant glycosyl amino acids using a non-natural amino acid as the glycosyl acceptor is described. The procedure involves a glycosylation reaction of a suitable carbohydrate donor with Fmoc-l-hydroxynorleucine benzyl ester. This reaction results in the direct incorporation of the amino acid moiety. The acceptor can be used for the preparation of α- or β-O-linked glycosides depending upon the nature of the glycosyl donor. This method has been applied in the synthesis of six different tumor-associated carbohydrate antigens.     

A new access to 3,5-disubstituted piperazinones via Pd(0)-catalyzed amination

An original synthetic route toward 3,5-disubstituted piperazinones has been developed. The method relies upon a 6-exo intramolecular process between a sulfonylated nitrogen atom of amino acid derivation and an η³-allyl-palladium moiety. This cyclization process generates the two possible (cis and trans) diastereoisomers whose ratio depends on the amino acid employed. The bulkier the amino acid residue, the higher the observed cis:trans ratio. Convincing evidence for reversible intramolecular addition of the nitrogen nucleophile to the η³-allyl-palladium complex is put forward.     

Synthesis and structural characterization of N-para-ferrocenyl benzoyl amino acid ethyl esters and the X-ray crystal structures of the glycyl and (±)-2-aminobutyric acid derivative Fc-C6H4CONHCH(C2H5)CO2Et

A series of N-para-ferrocenyl benzoyl amino acid ethyl esters 1-8 have been prepared by coupling para-ferrocenyl benzoic acid with the amino acid esters using the conventional 1,3-dicyclohexylcarbodiimide (DCC), 1-hydroxybenzotriazole (HOBt) protocol. The amino acids employed in the synthesis were glycine, l-alanine, l-leucine, l-phenylalanine, β-alanine, 4-aminobutyric acid, (±)-2-aminobutyric acid and 2-aminoisobutyric acid. The compounds were fully characterized by a range of spectroscopic techniques such as NMR and mass spectrometry. In addition the X-ray crystal structures of the glycyl 1 and (±)-2-aminobutyrate 7 derivatives have been determined. Analysis of relevant fragments in crystal structures on the Cambridge Structural Database indicates a relative paucity of common fragments such as the α-aminobutyrate group in comparison to the glycyl moiety.     

Roseabol A,a New Peptaibol from the Fungus Clonostachys rosea

A new 11 amino acid linear peptide named roseabol A (1) and the known compound 13-oxo-trans-9,10-epoxy-11(E)-octadecenoic acid (2) were isolated from the fungus Clonostachys rosea. Combined NMR and MS analysis revealed that roseabol A (1) contained amino acid residues characteristic of the peptaibol family of peptides such as isovaline, α-aminoisobutyric acid, hydroxyproline, leucinol, and an N-terminal isovaleric acid moiety. The amino acid sequence was established by a combination of NMR studies and tandem MS fragmentation analyses, and the absolute configurations of the constituent amino acids of 1 were determined by the advanced Marfey’s method. Compound 2 showed inhibitory activity against Merkel cell carcinoma, a rare and difficult-to-treat type of skin cancer, with an IC₅₀ value of 16.5 μM.     

Synthese de polymeres a proprietes pharmacologiques: Introduction de sequence peptidique en chaine laterale

Amino acids have been introduced on to the side-chains of a polymer. Two schemes have been studied: the first involves the synthesis of a monomer containing the amino acid drug moiety and subsequent polymerization; the second depends upon chemical modification of a polymer with the amino acid drug moiety. The drugs used in this study are steroids (cholesterol testosterone). The amino acid moieties introduced on to the side-chains are L-lysine. The preparation of the drug containing the amino acid is done by reacting the chloroformate derivative of the steroid with the amine function of the lysine subsequent to the blocking of the amino acid as a copper complex. The methacrylic monomer is obtained by reacting methacryloyl chloride with the drug amino acid moiety. The polymers were characterized by i.r., NMR (¹H and ¹³C) and GPC. Pharmacological tests are being performed to observe the effect due to the hydrolysis of the drug or the amino acid drug in living organisms.     

Synthesis and antifungal activity of rhodopeptin analogues. 1. Modification of the east and south amino acid moieties

Structure-activity relationships of the east and south amino acid modified analogues of rhodopeptins, novel antifungal cyclic tetrapeptides isolated from Rhodococcus species Mer-N1033, have been investigated. It was observed that a basic amino acid moiety (lysine or ornithine) as the east amino acid and a hydrophobic and bulky neutral amino acid (i.e., gamma-methylleucine) as the south amino acid were indispensable structure motifs for antifungal activity of rhodopeptin analogues.     

Modeling the reactive properties of tandemly activated tRNAs

Tandemly activated tRNAs, bearing amino acid moieties at both the 2'- and 3'-positions of the 3'-terminal adenosine moiety (A(76)), have been shown to participate efficiently in protein synthesis [B. Wang, J. Zhou, M. Lodder, R. D. Anderson, III and S. M. Hecht, J. Biol. Chem., 2006, 281, 13865]. The mechanism by which such activated tRNAs are able to donate both amino acids to the growing polypeptide chain is not well understood. Here we report the chemical behavior and participation in protein synthesis of new bisaminoacyl derivatives of pdCpA and tRNA. Both amino moieties of the aminoacyl groups are shown to be important to enable participation in protein synthesis; paradoxically, they also confer an unanticipated chemical stability toward different nucleophiles. The results obtained suggest a model for participation of bisaminoacylated tRNAs in protein synthesis.     

Synthesis of new steroidal derivatives by the reaction of steroid-amino acid conjugates with N,N′-dicyclohexyl-carbodiimide. Unusual formation of steroidal imide derivatives

Several new steroid derivatives have been synthesised by the reaction of steroid-amino acid conjugates with N,N′-dicyclohexyl-carbodiimide. Selectivity of the reaction was found to depend greatly on the properties of the amino acid moiety. While the reaction of the glycine derivative led to the corresponding 5(4H)-oxazolone, an unusual imide formation together with an N-acylurea side product was observed in the case of conjugates of l-alanine, l-phenylalanine and l-methionine. The structures of the new products, steroidal imide and N-acylurea derivatives, were determined by various spectroscopic methods.     

Stereoselective synthesis of the hydroxy amino acid moiety of Al-77-B,a gastroprotective substance from Bacillus pumilus Al-77

The hydroxy amino acid moiety of Al-77-B (1) has been prepared as its protected form 2 from the (R)-glyceric acid derivative 3 in an efficiently stereoselective manner through the direct C-acylation using diphenyl phosphorazidate and the hydroxy-directed hydrogenation.     

Retention of stereochemistry in the microwave assisted synthesis of 1H-tetrazole bioisosteric moiety from chiral phenyl-acetic acid derivatives

Chiral substituted phenylethyl-1H-tetrazoles were built-up from the corresponding carboxylic acid derivatives by a useful three-step synthesis. The procedure, that preserves the chiral center from racemization, was successfully applied to a selection of several hit compounds by conversion of the carboxylic acid moiety to the nitrile derivatives and subsequent reaction with trimethylstannyl azide, under microwave conditions. A useful application to the corresponding tetrazole analogue has been found also in the conversion of the aminoacidic moiety like (R)-N-Cbz-phenylglycine showing a wide potential synthetic application.     

Enhancement in the rate of conversion of peptide Cys-Pro esters to peptide thioesters by structural modification

We previously reported that the peptide containing a Cys-Pro ester (CPE) moiety is spontaneously transformed into a peptide thioester via an N to S acyl shift followed by diketopiperazine formation. In an attempt to identify more reactive structures for the formation of a peptide thioester, we modified the CPE structure, in which the Pro residue in the CPE moiety was replaced with N-substituted glycine derivatives. These peptides were transformed into a peptide thioester more rapidly. Alternatively, the addition of an amino acid residue at the C-terminus of the CPE moiety also accelerated thioester formation.     

Solid-phase synthesis of 1,5-substituted 2-(N-alkylamino)-imidazolidin-4-ones

The solid-phase synthesis of 1,5-substituted 2-(N-alkylamino)-imidazolidin-4-one from resin-bound amino acid is described. Using a guanidinylating reagent in solution to form the guanidine moiety instead of resin-bound carbodiimide, an N-alkyl substitution is introduced specifically onto the 2-amino position. Combined with an alkylation step of the resin-bound amino acid prior to guanidinylation, all desired substitutions of the final products are achieved without racemization at chiral centers. This reaction sequence is also compatible with a variety of protected amino acid side chains.