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S Fermandjian

Publications and source records attributed to S Fermandjian.

18 recordsLinked to original sources
PubMed1992

The fine structure of two DNA dodecamers containing the cAMP responsive element sequence and its inverse. Nuclear magnetic resonance and molecular simulation studies.

1H and 31P n.m.r. (nuclear magnetic resonance) spectroscopy have been used in conjunction with molecular simulation to determine the structure of two DNA dodecamers. The first of these, CATGACGTCATG, contains the octameric sequence CRE (cAMP responsive element), while the second is the reversed sequence, GTACTGCAGTAC. Structure determination was based on both NOESY (nuclear Overhauser spectroscopy) derived distances and COSY (correlated spectroscopy) dihedral angle data. Access to the 31P spectra also allowed the epsilon backbone angles to be determined. Considerable care was taken in deriving structural parameters from the n.m.r. data and an excellent level of agreement is obtained with the simulated conformations. Both dodecamers are found to belong to the B-DNA family; however, there is a striking difference between the CRE sequence and its inverse, the former conformation alone showing a strong structural heterogeneity.

Base Sequence↗
PubMed1992

Probing intercalation and conformational effects of the anticancer drug 2-methyl-9-hydroxyellipticinium acetate in DNA fragments with circular dichroism.

Circular dichroism was applied to the analysis of drug-DNA associations. With the octanucleotide d(TGACGTCA) (octanucleotide I), which is the cAMP-responsive element (CRE) in gene promoters and its reverse d(ACTGCAGT) (octanucleotide II), it was demonstrated that the anticancer polyaromatic agent celiptium intercalates into DNA base pairs with its long direction perpendicular to both the DNA-helix axis and the base-pair long axis and induces larger conformational changes in the CpG-containing octanucleotide I CRE than in its reverse-sequence octanucleotide II. It was concluded that CD is a powerful and sensitive technique to discriminate between drug-binding modes of DNA, to define the geometry of the chromophore inserted into base pairs and, finally, to measure sequence-dependent conformational changes induced by intercalation in DNA. We anticipate that these studies will contribute to a better understanding of the molecular bases that underlie the mechanism of action of those cytotoxic drugs which interfere with the DNA-nuclear-protein recognition.

Antineoplastic Agents↗
PubMed1979

Conformational features of bradykinin. A circular dichroism study of some peptide fragments and structural analogues of bradykinin.

The vasoactive hormone bradykinin, its N-and C-terminal fragments and some structural analogues were studied by Circular Dichroism. Conformational features of the peptide can be detected by comparative analysis of the various CD spectra recorded as a function of aqueous pH, solvent and temperature. It is shown that the two biologically essential arginine residues (Arg1 and Arg9) are important for the specific folded bradykinin conformation. Differences between bradykinin, its fragments and analogues become clearly established in conformational terms, and are discussed in relation to the biological activity of these peptides.

Bradykinin↗
PubMed1978

Conformation of corticotropin. An infrared spectrometry study of hydrogen exchange kinetics.

1H--2H exchange kinetics of the peptide hydrogens in corticotropin have been examined in 2H2O and CF3C2H2O2H solutions by means of infrared absorption measurements. In aqueous solution, around pH 3, the experimental data suggest a partially ordered structure, since in the two corticotropins 1--24 and 1--32 about 6 slowly exchanging peptide protons are numbered. These might belong to the N-terminal part of the molecule. The C-terminal 25--32 octapeptide segment appears to be unordered and slightly destabilizes the overall hormone conformation. For corticotropin1--24 in CF3C2H2O2H, the qualitative interpretation of infrared spectra and the quantitative analysis of exchange data give evidence of a strong stabilization: a predominantly alpha-helical structure is induced by trifluoroethanol.

Adrenocorticotropic Hormone↗
PubMed1978

A proton NMR investigation of proline-24 cis-trans isomerism in corticotropin 1-32 and related peptides.

250 MHz 1H-NMR studies performed on aqueous solutions of corticotropin1-32, corticotropin1-24, corticotropin15-32, corticotropin20-32 and corticotropin15-24 have allowed the location and the subsequent assignment of the signals of Tyrosine-23 aromatic protons and valine-22 methyl protons. These signals are sensitive to the geometry of proline-24, clearly transcribe its isomerism and yield the ratio of the cis-trans conformers. It is concluded that for large peptides in specific cases, the proton signals of side chains can be used to probe the backbone conformation.

Adrenocorticotropic Hormone↗
PubMed1977

Conformational features of bradykinin. A circular dichroism study of the aromatic side-chains.

The circular dichroism (CD) of the peptide hormone bradykinin and its analogues, [Phe(H4)5]-bradykinin, [Phe(H4)8]bradykinin, [Phe(H4)5,8]bradykinin, [TyrOMe5]bradykinin, [TyrOMe8]bradykinin and [TyrOMe5.8]bradykinin, is described. The comparison of the CD spectra of these analogues with each other, recorded under a variety of conditions (pH, solvent, temperature), allows the monitoring of the behaviour of the aromatic side-chains (phenylalanine, tyrosine) and an estimation of their respective spectral contributions in both spectral regions (320-250 nm, 250-190 nm) with good precision. Conformational non-equivalence of the residues Phe-5 and Phe-8 together with some overall conformational features of bradykinin are thus established.

Bradykinin↗
PubMed1977

Quantitative 250 MHz proton magnetic resonance study of hydrogen-deuterium exchange. Angiotensin II hormone in trifluoroethanol.

Hydrogen-deuterium exchange kinetics of (Asn1-Val5) angiotensin II has been investigated by proton magnetic resonance at 250 MHz in deuterated trifluoroethanol, as an approach to the "in situ" hormone conformation. An interactive program was specially developed to perform the data analysis on a computer similar to those used for spectroscopic data acquisition. Nine exchange sites are evidenced and characterized by their individual kinetic parameters. Three of them are assigned to peptide NH hydrogens, and the six remaining to slowly exchanging side chain protons. At 11 degrees C, more than three peptide hydrogens, sterically hindered or involved in hydrogen bonds, do not exchange. These results corroborate previous circular dichroism and infrared investigations performed in the same solvent, and suggest a family of well-folded conformations, stabilized in trifluoroethanol by internal hydrogen bonds, involving both the backbone and the side chain hydrogens.

Angiotensin II↗
PubMed1977

Influence of hydrogen bonding on the rotamer distribution of the histidine side chain in peptides: 1H NMR and CD studies.

Both 1H NMR and circular dichroism pH titration studies on histidine, His-Gly, Gly-His and Gly-His-Gly indicate that the side-chain spatial orientation depends strongly on the vicinal charges. The arrangement of the imidazole side-chain (rotamer population) is shown by the histidine beta and beta' and the glycine methylene proton chemical shifts as well as the vicinal 1H-1H coupling constants 3JCalpha-H-beta-H, beta'-H. For His-Gly and Gly-His-Gly a good correlation can be found between the ionization of the glycine COOH group and the increase of rotamer III (g-g) which is also visualized by circular dichroism through an enhancement of the ellipticity at 212 nm. In these two peptides a hydrogen bond between the imidazolium and the carboxylate group is supposed to stabilize rotamer III at pH 4-5.

Circular Dichroism↗
PubMed1977

Circular dichroism studies of angiotensin II and analogues: effects of primary sequence, solvent, and pH on the side-chain conformation.

Conformational aspects of the pressor hormone angiotensin II and 11 of its structural analogues were studied by circular dichroism. Each position of the peptide was singly substituted with an aliphatic residue and alterations of the CD spectra of the resulting analogues in the peptide and aromatic spectral regions (320-250 nm, 250-190 nm) were examined. The spectra of these peptides in 2,2,2-trifluoroethanol solution permit estimation of the relative importance of the various side chains in maintaining the backbone conformation of the hormone. The evolution of the CD spectra in both spectral regions of the peptides in aqueous solution during a titration from pH 1 to pH 12 makes it possible to elucidate further the role of ionizable groups and their interaction with aromatic amino acids such as tyrosine. The results obtained indicate that substitutions in aspartic acid 1, proline 7, and phenylalanine 8 of angiotensin II entail changes in the backbone conformation. On the other hand, the side chains of valine 3, isoleucine 5, and the biologically essential histidine 6 serve mainly to correctly align the phenolic ring of tyrosine in position 4.

Amino Acid Sequence↗
PubMed1976

Conformational studies of corticotropin1-32 and constitutive peptides by circular dichroism.

Circular dichroism spectra on corticotropin1-32 and its constitutive N-, and C-terminal peptides are determined in water and trifluoroethanol under several conditions in the aromatic and peptide spectral regions. Furthermore, the effects of pH and varied mixtures of water-trifluoroethanol are examined on the corticotropin1-32 molecule. The results show that the N- and C-terminal series have a different behaviour in both aqueous and organic media. Corticotropin and the former peptides display "random" spectra in water, and alpha-helix type spectra in trifluoroethanol, while the latter have "random" spectra in both solvents. In the holopeptide corticotropin, the side chain-side chain effects, as reflected by the titration curves obtained from variations in the aromatic region, support the idea of an helical organization of part of the backbone even in aqueous solution. When going from water to trifluoroethanol corticotropin1-32 undergoes a conformational change which leads to an alpha-helix, following a linear pathway. These results, together with other observations, indicate the possible role of the conformation of corticotropin molecules in their biological life.

Adrenocorticotropic Hormone↗
PubMed1976

Circular-dichroism spectra of truncated and other analogs of angiotensin II.

Circular dichroism spectra on angiotensin II and analogs, and its truncated N-terminal and C-terminal peptides were determined in fluroinated alcohols under several conditions in the peptide or aromatic spectral regions. The following conclusions were suggested: (a) evidence for a beta structure for angiotensin II; (b) evidence for a folding at the N-terminal and C-terminal part of the molecule; (c) an interaction involving the C-terminal residue which decreases progressively when phenylalanine is replaced by isoleucine and then by alanine; (d) the N-terminal amino acid seems to play an important role in the overall conformation of the molecule possibly by interacting with the C-terminus, its absence in the 2 -- 8 heptapeptide giving rise to a more pronounced signal than angiotensin II; (e) in trifluoroethanol the conformation of these peptides is well defined and fits well with observed structure-activity relationships and observed binding data. There is a loss of this relationship when these solvents are diluted with water.

Amino Acid Sequence↗
PubMed1975

13C-nuclear magnetic resonance studies of 85% 13C-enriched amino acids and small peptides. pH effects on the chemical shifts, coupling constants, kinetics of cis-trans isomerisation and conformation aspects.

The 13C chemical shifts of several 85% 13C-enriched amino acids and small peptides were studied as a function of pH. The results show that the chemical shifts of carbon atoms of ionizable groups vary significantly within the zone of their pK. Generally with the pH GOING FROM 7 to 1 all the deltaC are shifted more or less upfield with the exception of the carbonyl group carbon of the second last residue which is shifted slightly downfield. This suggests the formation of an hydrogen bond at acid pH involving in a seven-membered ring the C=O in question and the COOH terminal. The percentage of cis and trans conformers of glycyl-L-proline and glycyl-L-prolylglycine were studied as a function of pH. The trans form is always preponderant whatever the pH. The accessibility of the carbonyl group to protonation of the proline residue strongly influences the cis-trans equilibrium. Thus, with the pH varying from 7 to 1, the trans isomer changes from 61 to 85% for glycyl-L-proline and only from 77 to 80% for glycyl-L-prolylglycine. The proton NMR studies underline the important differences existing between the two molecular forms of glycyl-L-proline. The cis conformation is characterized with regard to the trans form by the non-equivalence of the alpha-protons of the glycine residue, by a lower pK(1) and by a larger deltadeltaHalpha of the proline residue as a function of pH. These results could suggest an end-to-end interaction in the cis form of the glycyl-L-proline molecule. The 13C-13C coupling constants were also studied as a function of pH. The results show that J(Co-Calpha) of a C-terminal residue, varying from 5 to 6 Hz and reflecting thhe pK of the carboxylate group, is a linear function of delta(Co) and delta(Calpha) as in the case of the amino acids. The total variation of the electron density of those two carbons in an amino acid is approximately 40% weaker than in a C-terminal residue. The charge distribution along the Calpha-C(o) bond, however, is practically the same in both cases. Finally the ratios of the conversion rate constants of the two isomers cis-trans of glycyl-proline were calculated at different pH values; the relations between the isomer percentages and delta(Co), delta(Calpha) on the one hand and the J(Co-Calpha) on the other were established.

Amino Acids↗
PubMed1975

13C-nuclear magnetic resonance study of [85% 13C-enriched proline]thyrotropin releasing factor: 13C-13C vicinal coupling constants and conformation of the proline residue.

To understand fully interactions between peptides and cellular receptors, peptide side chain conformation must be defined. In many cases the complexity of proton nuclear magnetic resonance (NMR) prevents this but the present work demonstrates this problem can be solved by using 13C enrichment. Selective 13C enrichment of a natural peptide hormone has been achieved by preparing [85% 13C-enriched proline]thyrotropin releasing factor which was examined by 13C NMR spectroscopy at various pH values. Because of the 13C enrichment, one-bonded and three-bonded (vicinal) 13C-13C coupling constants have been determined. The latter vary from 0 to 5 Hz and show bond angle dependence. These data indicate that in this hormone the pyrrolidine ring is not free but fixed in the Cgamma-endo puckered conformation. It has also been possible to assign chemical shift values for a second order 13C NMR spectrum.

Carbon Isotopes↗