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Biomedical subjects

A Brack

Publications and source records attributed to A Brack.

At least 73 records · Page 4Linked to original sources
PubMed1987

Search for catalytic properties of simple polypeptides.

Simple polypeptides were used as possible supports for nucleotide polymerization, in the absence of any preformed polynucleotide template. Sequential copolymers of alanine and glycine, water soluble polypeptides based on arginine and poly(Glu-Ser-Glu) have been tested. No catalytic effect has been found although poly(Glu-Ser-Glu) favors the 2'-5' internucleotide linkage. More interestingly, polypeptides containing arginine residues strongly accelerate the hydrolysis of oligoadenylic acids. The influence of pH, temperature, nature of the buffer and polypeptide sequence was investigated.

Adenine Nucleotides↗
PubMed1987

Search for chiral molecules and optical activity in extraterrestrial systems. Example of Titan.

One of the main characteristics of terrestrial life is the role of optically active organic substances. Thus a search for chiral compounds and optical activity on an extraterrestrial body may give an indication of the presence of life, either fossilized or still in existence. If only abiotic conditions are prevailing the same search may still provide interesting information on the possible origins of homochiral families of biomolecules on Earth (e.g. the amino acids). In this respect, Saturn's satellite Titan is exemplary. A list of some of the most simple chiral derivatives devoid of oxygen atoms possibly present on Titan is presented. The interest of an investigation of optical activity is discussed taking into account some significant parameters. This raises numerous difficult technical problems which once solved may be helpful for further exploration of other planets.

Biological Evolution↗
PubMed1987

Synthesis of a new carrier for immunization: polytuftsin. Two examples of its use with peptides selected in the hepatitis B surface antigen.

Sequential poly(Arg-Thr-Lys-Pro) consisting mainly of the repeat of tuftsin Thr-Lys-Pro-Arg was synthesized by condensing the p-nitrophenyl ester of Arg(HCl)-Thr-Lys-(2-Cl-Z)-Pro in the presence of HOBt. Two haptenic sequences of the Pre-S region of hepatitis B virus antigen (10-26 and 39-55) were prepared by solid phase and coupled to polytuftsin via glutaraldehyde. The peptides, either free or coupled to polytuftsin, were administrated to mice and the antisera were assayed by ELISA. Coupling the peptides to the polypeptide significantly improved the anti-peptide antibody titer in Freund complete adjuvant or in NaCl 0.9%. Cross-reaction between antibodies induced by the peptides and the native protein was also improved. Polytuftsin alone is very poorly immunogenic.

Animals↗
PubMed1986

Early emergence of protein precursors.

For the emergence of protein precursors essential to primitive cells three prerequisites must have been fulfilled: selective aqueous polymerization of proteinaceous amino acids from a complex mixture of small organic compounds, selection of homochiral amino acid sequences and catalytic activity with respect, more precisely, to information transfer processes.

Amino Acids↗
PubMed1985

Interaction of DNA with lysine-rich polypeptides and proteins. The influence of polypeptide composition and secondary structure.

Using X-ray diffraction we have studied fibres obtained from complexes of DNA with lysine-rich polypeptides and with proteins that have different conformations, to ascertain whether the conformations of the polypeptides and the DNA are maintained upon interaction. Substances investigated include N-acetyl-Lys-Ala-Tyr-Ala-Lys-ethylamide, random poly(Leu50, Lys50), sequential poly(Leu-Lys), poly(Val-Lys), poly(Ala-Lys), poly(Lys-Ala-Ala-Lys), poly(Lys-Ala-Ala), poly(Lys-Leu-Ala), poly(Lys-Ala-Gly), protein phi 0 from sea cucumber spermatozoa, histone H1 and two fragments of this protein obtained by chemical cleavage. In general, the B form of DNA with ten base-pairs per helical turn is maintained upon interaction at high levels of humidity. The A form is never observed; it appears to be forbidden in a protein environment. No evidence for transition into any novel DNA conformation has been observed, although the B form is altered in some cases, in particular upon dehydration. Such alteration occurs always in the sense of tightening the double helix, so that the number of base-pairs per helical turn diminishes. The polypeptides may interact with DNA in both the alpha and beta conformations. We have found different types of complexes in which either a monolayer or a double layer of beta-pleated sheets is intercalated between layers of DNA molecules. Alternatively, the polypeptide chain may be wrapped around the DNA, following one of the grooves. The polypeptide conformation may be either maintained or changed upon interaction. The charge density of the polypeptide is an important parameter of the interaction. When it matches the charge density of the DNA, the polypeptide conformation is maintained in most cases; otherwise it is modified. The globular part of histone H1 gives a unique X-ray pattern upon interaction, indicative of a loss of order of DNA in the complex. On the other hand, the C-terminal part of histone H1 gives a very well-ordered complex, similar to a nucleoprotamine, in spite of its lower charge density.

Amino Acid Sequence↗
PubMed1982

Aqueous polymerization of L-amino acid active esters in bicarbonate solution via Leuchs' anhydrides.

Aqueous polymerization of p-nitrophenyl esters of proteinaceous alpha-amino acids is much more efficient in the presence of sodium hydrogen carbonate than in the presence of sodium hydroxide for a given pH. Evidence is presented for the intermediary formation of Leuchs' anhydride in the presence of bicarbonate anions. The prebiotic significance of such a mechanism favouring the polymerization of proteinaceous alpha-amino acids, i.e. C alpha-mono-substituted amino acid, is discussed.

Amino Acids↗
PubMed1980

Beta-Structures of polypeptides with L- and D-residues. Part III. Experimental evidences for enrichment in enantiomer.

It was previously shown that nuclei of beta-sheets surrounded by unordered segments are formed in polypeptide chains built up with alternating hydrophobic and hydrophilic residues and containing both L- and D-enantiomers. It was also established that segments of residues having the same configuration tend to segregate in these nuclei when the starting composition of stereomonomers departs from the racemic mixture. Soft acidic hydrolysis of these polymers has been studied. Kinetic measurements show two pseudo first order rate constants, in agreement with the existence of two conformational species. The unordered part of the chains is hydrolyzed more rapidly, allowing the isolation of a beta-fraction enriched in one enantiomer. Thus, a plausible process of enrichment in enantiomer during prebiotic evolution has been described, which however does not explain the preference of one enantiomer over the other one.

Chemical Phenomena↗
PubMed1979

Beta-structures of polypeptides with L-and D-residues. Part I. Synthesis and conformational studies.

A series of five alternating poly(leucyl-lysyl) samples with varying amounts of L-and D-residues randomly distributed along the chain, but evenly shared out amongst leucyl and lysyl residues were synthesized by condensation of a mixture of the four diastereoisomeric dipeptide p-nitro-phenylesters. Their behavior in aqueous solution at various ionic strengths was studied by infrared spectroscopy which allowed measurement of the total amount of beta-structures, and by circular dichroism which gives the excess of L-residues over D-residues in the same structures. Comparison with the properties of the all L-poly(Lys-Leu-Lys-Leu) shows that incorporation of a few D-residues in a L-chain seems to reduce the width of the beta-sheets obtained in presence of salt. Higher proportions of D-isomers prevent the coil leads to beta transition from occurring when the ionic strength is increased except for segments containing at least 6 to 7 adjacent residues of the same configuration.

Circular Dichroism↗
PubMed1979

Beta-structures of polypeptides with L-and D-residues. Part II. Statistical analysis and enrichment in enantiomer.

The possible formation of beta-structures from polypeptide chains with L-and D-Residues randomly distributed was statistically analyzed within the frame of two hypotheses. Firstly, only those segments containing residues of identical chirality can associate to form antiparallel beta-structures, and secondly these segments must have a minimum length. The influence of different factors was examined: initial ratio of the L-and D-monomer, minimum length required for the segments to be incorporated into beta-sheets, average length of the peptide molecules, and stereoselectivity in the course of the polymerization process. The results show that in all cases nuclei of beta-sheets surrounded by random coil segments are formed, the optical activity of which very increases to purity when the initial ratio of monomers deviates from the racemic mixture. This suggests experiments to enrich the system in one enantiomer. Comparison is made with the corresponding behavior and properties of the alpha-helical structure.

Isomerism↗
PubMed1978

Synthesis and beta-conformation of copolypeptides with alternating hydrophilic and hydrophobic residues.

Copolypeptides with alternating hydrophilic and hydrophobic residues were prepared, and their ability to form beta-structures in aqueous solutions was investigated by circular dichroism. Optically pure samples of poly (Lys-Leu-Lys-Leu) and poly (Leu-Glu-Leu-Glu), obtained via the 2-hydroxyphenyl esters, undergo a coil-to-beta transition in presence of salt. The beta-structures obtained under identical conditions with partially racemized samples of poly (Leu-Lys)Np and poly (Leu-Glu)Np, prepared by polycondensation of the corresponding dipeptide p-nitrophenyl esters, appear to be less regular. Non-alternating poly (Gly-Lys-Leu-Lys-Leu) does not form beta-structures in presence of NaCl as does alternating poly (Lys-Leu-Lys-Leu) indicating that the amino acid sequence can dramatically change the tendency to form beta-structures.

Amino Acid Sequence↗
PubMed1977

beta-structures of alternating polypeptides and their possible role in chemical evolution.

The tendency of copolypeptides with alternating hydrophilic and hydrophobic residues to form water soluble beta-structures in presence of salt, already described for poly(Val-Lys) (Brack and Orgel, 1975), was generalized to optically pure poly(Lys-Leu-Lys-Leu) and poly(Leu-Glu-Leu- G lu). Substitution of about 10% of L-lysyl residues by their enantiomers did not prevent the coli to beta transition but had nervertheless a sensitive effect on the beta-structures. Disruption of the alternation by insertion of extra glycyl or L-prolyl residues as in poly(Gly-Lys-Leu-Lys-Leu) and poly(Pro-Lys-Leu-Lys-Leu) decreased dramatically the tendency to form beta-structures. However, by using strong interaction ions such as perchlorate ions or by lengthening the alternating sequences as in the semi-random copoly(Gly-Lys-Leu-Lys-Leu1, Lys-Leu-Lys-Leu1) and copoly(Pro-Lys-Leu-Lys-Leu1, Lys-Leu-Lys-Leu1) it was possible to obtain soluble beta-structures which showed differences in the CD spectra. The binding properties of the beta-surface are examined.

Circular Dichroism↗
PubMed1977

Identification of beta,beta-turns and unordered conformations in polypeptide chains by vacuum ultraviolet circular dichroism.

Different conformations of polypeptides were characterized by measurements of the circular dichroism (CD) extended into the vacuum ultraviolet region. (i) The linear beta-pleated sheet structure was characterized in a broad ultraviolet region down to 165 nm by examination of copolypeptides composed of alternating hydrophobic and hydrophilic amino-acid residues, e.g., poly(Lys-Leu-Lys-Leu). A short-wavelength intense band was found at about 169 nm, which is characteristic of beta-pleated sheet conformation. (ii) The beta-turns were experimentally measured using poly(Ala(2)-Gly(2)) in a broad spectral region down to 165 nm with accuracy. The observed CD spectrum is in excellent qualitative agreement with the theoretical curve calculated by Woody for the beta-turns of type II and/or I of Venkatachalam. The similarity in shape between the theoretical curve and the observed CD spectra suggests a dominance of beta-turn segments in the poly(Ala(2)-Gly(2)) structure. The presence of beta-turns in poly(Ala(2)-Gly(2)) is also in agreement with the characterization of this polypeptide by solid state methods (electron microscopy and x-ray diffraction). The CD spectrum of beta-turns is characterized by a very intense band at 207.5 nm and strong negative bands at 191 and 169 nm. Copolypeptides such as poly(Ala(2)-Gly(3)) and poly(Ala(3)-Gly(3)) yielded a similar type of CD spectrum, analysis of which indicates that a large fraction of their residues is contained in beta-turn regions. (iii) The CD spectrum of the unordered chain of these alternating copolypeptides in salt-free solution is observed in the vacuum ultraviolet region.

Circular Dichroism↗
PubMed1975

Beta structures of alternating polypeptides and their possible prebiotic significance.

A survey of the commonest amino acids formed in prebiotic conditions suggests that the earliest form of genetic coding may have specified polypeptides with a strong tendency to form stable Beta-sheet structure. Poly(Val-Lys), like other polypeptides in which hydrophobic and hydrophilic residues alternate, tends to form Beta structures. We show that bilayers with a hydrophobic interior and a hydrophilic exterior may be present in aqueous solution.

Chemical Phenomena↗