Márton Kajtár

Complex formation of phenolphthalein and some related compounds with β-cyclodextrin

The complex formation of phenolphthalein and β-cyclodextrin (cyclohepta-amylose) has been investigated by spectrophotometric, c.d., and potentiometric methods. It has been shown that complexes are formed with the protonated and dissociated forms of phenolphthalein as well; the dianion is complexed in alkaline solution in a colourless form. The complexes formed have the largest stability constants among cyclodextrin complexes known up to now. The unusual stabilities and colour change can be explained by the combined effect of the accessibility of the phenolic-phenolate moiety and presence of the carboxy–carboxylate group simultaneously, providing optimal space filling and the possibility for the cyclodextrin molecule to interact with three functional groups of phenolphthalein at the same time.

Studies on the conformation of β-endorphin and its constituent fragments in water and trifluoroethanol by CD spectroscopy

Structure-function studies on P-LPH fragments have revealed that the in vitro opiate agonist activity is an exclusive property of fragments containing the complete structure of Met-enkephalin (LPH (61-65)) [ 1 ] at their NH*-terminus and that the biological potency is a function of the chain length of the peptides [2-61. Peptides intermediate between Metenkephalin and LPH (61-9 1) (named fl-endorphin by Li and Chung, [7] ) were found to be less potent than Met-enkephalin in different in vitro bioassays [2-61. Elongation of the peptide chain of LPH (61-79) by addition of the 12 COOH-terminal residues of fl-LPH [4-61 to form P-endorphin caused a dramatic change in the biological properties of the molecule. Among all the fragments studied so far, /3-endorphin is the most active in receptor binding [2,7] in guinea-pig ileum bioassays [3-61 and the least active in mouse vas deferens test [5,6]. In addition, &endorphin exerts the most profound analgesic [2,4,8,9] and behavioral effects [ 10,l l] when administered intraventricularly [2,4,8,10,11] or intravenously [9] to different animals. From the above relationships the impression has

The utility of the four-dimensional ramachandran map for the description of peptide conformations

Abstract On the basis of multidimensional conformational analysis a two-dimensional Ramachandran map of a single amino acid unit in a peptide is expected to have, under ideal conditions, 3 2 =9 distinct minima according to the following pattern: γ D δ D α L ϵ D β DL ϵ L α D δ L γ L Consequently, a dipeptide unit, which corresponds to a four-dimensional Ramachandran map, is expected to have 3 4 =81 distinctly different minima, under ideal conditions. Some of these minima may be labelled γ L γ L ,γ L δ L ,γ L ϵ L ,γ L α L ,γ L α D etc. It appears that the “unordered” conformations as well as the familiar “ordered” secondary structural elements such as α-helix, β-pleated sheet or the different types of turn in proteins might be related to the above 81 conformations of the dipeptides. This recognition leads to a system of conformational classification that may have far-reaching consequences for our understanding of the secondary and tertiary structures of peptides and proteins.

Chiroptical properties and solution conformations of protected endothiodipeptide esters

Abstract The syntheses and CD spectra in different solvents are described for four series of N-benzyloxycarbonyl-endothiodipeptide esters of types a - d with Ala, Val, Phe and Pro residues. Difference 1 H NOE and IR measurements were also performed on selected models. The spectroscopic evidence pointed to the existence of two main conformers in solution. Conformation A, predominating in nonpolar solvents, can be characterized as a folded C 7 C 5 form with a bifurcated system of intramolecular H-bonds formed by the thioamide N-H and the CO groups of the N-terminal urethane and the C-terminal ester moieties. Conformation B, the major conformation in H-bond-accepting solvents such as DMSO, is more extended and flexible in the N-terminal region and assumes a “proline-like” rotamer state (φ 2 ~ -60°) at the C-terminus. The sign and magnitude of the Cotton effect due to the n →π * transition (near 350 nm) can be rationalized with an octant-like sector rule. The optical activity of the π→π * transition is determined in part by exciton interaction of the thioamide with the urethane and/or ester chromophores. Through application of the sector rule, finer details of the correlation between the chiroptical properties and the conformation can be explained.

Synthese des immunspezifischen, polypeptid-artigen haptens der anthrax-subtilis bacillengruppe. Ein synthetischer beweis der konstitution der natürlichen polyglutaminsäuren☆

Zusammenfassung Es wurde die Synthese der γ-Poly- l -glutaminsaure (IIIa), γ-Poly- d -glutaminsature (IIIb) und der mosoiden γ-Poly-glutaminsaure (IIIc) durchgefuhrt. Als Schlusselsubstanz der Synthese diente der γ-Glutamyl-glutaminsaure-αα′-dimethylester (I) der l - l Form (Ia), d - d -Form (Ib) bzw. l - d -Form (Ic); diese drei Startdipeptide wurden aus l - bzw. d -Glutaminsaure in mehreren Schritten aufgebaut. Die intermolekulare Polyacylierung der bifunktionellen Startdipeptide, die zur Bildung des γ-Poly-glutaminsaure-α-methylesters (II) der entsprechenden Konfiguration fuhrte, liess sich auf viererlei Weise—durch Aktivierung der Carboxyl-bzw. Aminogruppe—bewirken. Nach der alkalischen Verseifung der Polyester (II) wurden die entsprechenden γ-Poly-glutaminsauren uber ihre schwerloslichen Kupfer(II)-salze abgesondert und durch Dialyse gereinigt. Der chemische und der von Prof. G. Ivanovics durchgefuhrte serologische Vergleich der γ-Polyglutaminsauren verschiedener Konfiguration mit dem Anthrax-Polypeptid und dem Subtilis-Polypeptid brachte—in ubereinstimmung mit der fruher mittels Abbau durchgefuhrten Konstitutionsermittlung—den Beweis, dass das Anthrax-Polypeptid die Konstitution der γ-Poly- d -glutaminsaure innehat. Da ausser der γ-Poly- d -glutaminsaure auch die mesoide γ-Polyglutaminsaure mit Antianthrax-Immunseren eine Prazipitationsreaktion zeigte, ist es nicht ausgeschlossen, dass in den Peptidketten des Subtilis-Polypeptids d - und l -γ-Glutamylreste vergesellschafter vorkommen. Durch die Synthese der γ-Poly- d -glutaminsaure (=Anthrax-Polypeptid) wurde zum ersten Mal die Vollsynthese eines naturlichen Haptens verwirklicht.

Synthesis and rearrangement of 13-thiaprostanoids

Abstract Thiaprostanoids 13 were prepared by conjugate addition of mercaptane 6 to cyclopentenones 12 and 20. Novel rearrangements of these compounds to 14 and 15 were interpreted as enolate induced [1,5]-sigmatropic shift on the corresponding dehydration products 16. Preparation of the various substrates and structural elucidation of new products are described.

Induced circular-dichroism spectra of complexes of cyclomalto-oligosaccharides and azobenzene derivatives

Abstract The circular-dichroism spectra of the inclusion complexes of 9 types of cyclodextrin (CDs) with 6 kinds of azobenzene derivatives generally show a single peak, but sometimes form a splitting pattern in the first π → π* region. All single patterns show a positive sign; indicating that the long and slim azobenzene derivatives are incorporated into the cavity from the long-axis side. The splitting patterns change in sign and magnitude according to the substitution on the component molecules and establish the formation of various stacking modes. Plots of the lengths of the azo dyes vs. the molar circular-dichroism coefficients suggest that the substituent on the CD torus is an important factor in causing splitting and deciding the sign of the split-type Cotton effects. The foregoing splitting may arise from exciton interaction of two molecules of the chromophoric dye each in the form of a 1:1 complex and in the cyclomaltooctaose (γCD) complex.

The sesquiterpene lactones from achillea fragrantissima, I. Achillolide A and B, two novel germacranolides

Abstract With the aid of one- and two-dimensional multipulse NMR techniques the structure of two novel sesquiterpene lactones from Achillea fragrantissima growing in Israel were elucidated and their conformational behaviour investigated. Although both compounds are closely related in their structures their CD spectra indicate that they belong to different enantiomeric series.

THE ROLE OF SULPHATION OF GLYCOSAMINOGLYCANS IN THEIR STRUCTURAL AND FUNCTIONAL CHARACTERISTICS

The CD spectra in the far ultraviolet and the CD and ORD spectra of methylene blue-complexes (MB-complex) of glycosaminoglycans (GAG) with different sulphate contents were studied in comparison with their effect on the in vitro formation of collagen fibres. The following polyanions were investigated: Chondroitin sulphate-A with different sulphate contents, oversulphated chondroitin sulphate, heparin and dextran sulphate and their desulphated derivatives. It was observed that the MB-complex of polysaccharides with the same backbone structure, but with different sulphate contents might show ORD and CD spectra of exciton type, but of inverse sign. This phenomenon was interpreted on the basis of different types of aggregation of dye molecules bound to the polysaccharides. The biological effect of GAG changed also with the sulphate content. This suggests that it is the extent of sulphation rather than the glycosidic structure of GAG which determines their chiroptical and functional properties.

Induced circular-dichroism spectra of complexes of cyclomalto-oligosaccharides and azo dyes containing naphthalene nuclei☆

Abstract In the circular-dichroism spectra of inclusion complexes of 7 types of cyclodextrin (CDs) with 6 kinds of azo dyes containing the naphthalene nucleus, the direction of inclusion and the stacking mode may be elucidated from patterns in the u.v. and the first π→π * regions. The patterns in the former region indicate that the naphthalene fragment in almost all of complexes is incorporated equatorially into the cavity. Those azo dyes that have a tight fit in the CD cavity exhibit exciton interaction between two molecules of the chromophoric dye included in the complexes. The spectral pattern changes in sign according to the inclusion mode of the guest molecules and the angle between the chromophores. For example, the spectral pattern of the Orange II-cyclomaltoheptaose (β CD) complex indicates that the naphthalene nucleus is included axially, and that the angle between two molecules of the azo dye is >90°. On the other hand, the spectral pattern of the Croceine Orange-DM-β CD complex indicates equatorial inclusion and a stacking angle of