Showing papers on "Side chain published in 1981"
TL;DR: Equilibria of distribution of amino acid side chains, between their dilute aqueous solutions and the vapor phase at 25 degrees C, have been determined by dynamic vapor pressure measurements, and hydration potentials are more closely correlated with the relative tendencies of the various amino acids to appear at the surface of globular proteins than had been evident from earlier distribution studies on the free amino acids.
Abstract: Equilibria of distribution of amino acid side chains, between their dilute aqueous solutions and the vapor phase at 25 degrees C, have been determined by dynamic vapor pressure measurements. After correction to pH 7, the resulting scale of "hydration potentials", or free energies of transfer from the vapor phase to neutral aqueous solution, spans a range of approximately 22 kcal/mol. The side chain of arginine is much more hydrophilic than those of the other common amino acids, with an equilibrium constant of approximately 10(15) for transfer from the vapor phase to neutral aqueous solution. Hydration potentials are more closely correlated with the relative tendencies of the various amino acids to appear at the surface of globular proteins than had been evident from earlier distribution studies on the free amino acids. Both properties are associated with a pronounced bias in the genetic code.
853 citations
TL;DR: A [2Fe-2S] ferrodoxin from Spirulina platensis was crystallized in space group C2221 with cell dimensions of a = 62.32, b = 28.51, c = 108.08 A, and alpha = beta = gamma = 90.0 degrees.
Abstract: A [2Fe-2S] ferrodoxin from Spirulina platensis crystallized in space group C2221 with cell dimensions of a = 62.32, b = 28.51, c = 108.08 A, and alpha = beta = gamma = 90.0 degrees. X-ray structure analysis of the protein was carried out at 2.5 A resolution by the single isomorphous replacement method coupled with the derivative and the native anomalous dispersion methods. Phase angles of 2182 independent reflections were determined and their average figure of merit was 0.58. Each of 98 residues was superposed on the electron density sections enlarged to 2 cm/l A with a half-mirror device (Richards box). About 25% of the total residues form beta-structure and 10% fold in a tow-turn alpha-helix. A beta-barrel-like structure was found in the main chain fold. A polypeptide segment from residues 41 to 49 forms a loop structure outside the barrel. Two iron atoms of the [2Fe-2S] cluster are coordinated by three cysteines in the loop and by Cys-79. Hydrogen bonds of NH....S and OH....S stabilize the loop conformation. Most side chains are reasonably oriented in the molecule. The internal volume of the barrel is occupied by aliphatic nonpolar residues. All the charged groups are accessible to solvent molecules.
160 citations
TL;DR: It was concluded that the protein stabilization by polyols is a manifestation of polyol-induced strengthening of the hydrophobic interaction of protein molecules.
Abstract: The solubilities of several amino acids and diglycine have been measured in water and at several concentrations of methanol and various polyols (glycerol, erythritol, xylitol, sorbitol, and inositol). The solubility data were used to calculate the free energy of transfer of amino acid side chains and peptide group from water to the aqueous alcohol solutions. The results for methanol systems were similar to those reported for ethanol and dioxane systems. The free energy of transfer to aqueous solutions of linear polyols was positive for most nonpolar side chains and peptide group, but high concentrations of the polyols may disrupt the hydrophobic interactions of large nonpolar side chains. Moreover, the linear polyols appeared to stabilize the hydrophobic interaction more effectively and the peptide-peptide hydrogen bond less effectively with increasing hydroxymethyl chain length of polyols. A cyclic polyol, inositol, had a very strong stabilizing ability on hydrophobic interactions of nonpolar side chains, but it may act as a destabilizing reagent for peptide-peptide hydrogen bonds. From these results, it was concluded that the protein stabilization by polyols is a manifestation of polyol-induced strengthening of the hydrophobic interaction of protein molecules.
140 citations
TL;DR: A convenient method for the separation of molecular species of phosphatidylcholine by reversed-phase high performance liquid chromatography (HPLC) is described, finding the average HCN to be remarkably the same for all the three different naturally occurring sources considering a wide variety of different fatty acid compositions of each type.
131 citations
TL;DR: The increase in the susceptibility to chymotrypsin attack with an increasing spacing of the Y-NAp residue from the backbone of the polymer chains is demonstrated by comparing the kinetic data of copolymers containing -Gly-Gly
Abstract: A series of copolymers of N-(2-hydroxypropyl)methacrylamide were prepared, which contained side chains of the general formula -Gly-X-Y-NAp, where Gly ¨ glycine; X ¨ glycine, alanine, β-alanine, valine, leucine, isoleucine, phenylalanine; Y ¨ phenylalanine or tyrosine; NAp ¨ p-nitroanilide, the latter modelling biologically active compounds. The rates of chymotrypsin-catalyzed hydrolysis of p-nitroanilide groups at pH = 8,0 and 25°C were determined over a range of substrate concentrations to derive values for kcat and KM. The results allowed us to determine the influence of the structure of side chains on the rate of cleavage of Y-NAp. The increase in the susceptibility to chymotrypsin attack with an increasing spacing of the Y-NAp residue from the backbone of the polymer chains is demonstrated by comparing the kinetic data of copolymers containing -Gly-Gly-Phe-Phe-NAp, -Gly-Gly-Phe-NAp and -Gly-Phe-NAp side chains. Results obtained with α-chymotrypsin were compared with the cleavage of the above polymer substrates with chymotrypsin covalently bound to a copolymer of N-(2-hydroxypropyl)methacrylamide.
125 citations
TL;DR: In this paper, a radiation-induced graft copolymerization technique using various mixtures of 2-hydroxyethyl methacrylate (HEMA) and EHEMA was used as graft substrates, and the critical surface tension of each polymeric surface in air was estimated by the Zisman method.
120 citations
TL;DR: Partition coefficients in n-octanol-water have been determined for the naturally occurring and some synthetic α-amino acids using thin-layer chromatography in different solvent systems as discussed by the authors.
99 citations
91 citations
TL;DR: In this paper, a μ-oxo bridged model has been proposed for the complexes in haemerythrin and myohaemerythsrin on the basis of crystallographic studies of the proteins.
Abstract: Haemerythrin and myohaemerythrin are non-haem iron proteins utilized by several marine invertebrates in transporting and storing oxygen Haemerythrin is oligomeric [usually octameric, but also trimeric1,2, and tetrameric and dimeric (C A Appleby, personal communication)] whereas myohaemerythrin is a monomeric analogue of the haemerythrin subunit Physico-chemical investigations3–5 of these molecules have shown that (1) each subunit binds two iron atoms by means of amino acid side chains, (2) one molecule of O2 is bound to each binuclear iron centre, and (3) the iron atoms are in the +3 oxidation state in oxy and met forms of the proteins and +2 in deoxy Models have been proposed for the complexes in haemerythrin and myohaemerythrin on the basis of crystallographic studies of the proteins A μ-oxo bridged model (Fig 1a) has been proposed from the results of a crystallographic analysis of metazidomyo-haemerythrin from Themiste zostericola6 Based on a similar analysis of methydroxohaemerythrin from Themiste dyscritum, previously referred to as metaquohaemerythrin7, we proposed a confacial bi-octahedron model with no atom identified as a μ-oxo bridge (Fig 1b)8 Previously9, we stated that “at least one of the models is incorrect” In fact, neither completely accounts for the electron density from the present 22 A resolution difference map of the complex and surrounding electron density of metazidohaemerythrin from T dyscritum
85 citations
TL;DR: Surprisingly sharp lines in the 270-MHz proton NMR spectrum of the enzyme complex are attributed to remarkable conformational mobility of large regions of polypeptide chain carrying the lipoic acid residues, which would enhance the functional connection of active sites in a multisubunit structure.
Abstract: Recent studies of several small proteins by NMR spectroscopy and X-ray crystallography have clearly demonstrated significant internal mobility in their structures (see, for example, refs 1–9), which can involve not only amino acid side chains but also larger regions of polypeptide chain. Occasionally a plausible function for this mobility has been suggested1,9, but there has been no conclusive evidence for a direct connection between intramolecular mobility and a defined step in an enzymatic mechanism. The pyruvate dehydrogenase (PDH) multienzyme complex of Escherichia coli (molecular weight (Mr) 4.5–6 ×106) is one of the largest well defined assemblies of proteins known, comprising multiple copies of three different enzymes10,11. The substrate is carried in thioester linkage by lipoyl–lysine residues of the lipoate acetyltransferase component, the structural core of the complex. The lipoyl–lysine residues act as swinging arms, carrying substrate between the catalytic centres of the three enzymes12–15 and between lipoic acid residues attached to different subunits in the lipoate acetyltransferase core16–18. It has been conjectured that the lipoic acid-containing regions of polypeptide chain might be flexible19,20 and therefore able to increase greatly the effective radius of a swinging arm19. We report here unexpectedly sharp lines in the 270-MHz proton NMR spectrum of the enzyme complex that are attributed to remarkable conformational mobility of large regions of polypeptide chain carrying the lipoic acid residues. This mobility would enhance the functional connection of active sites in a multisubunit structure.
77 citations
TL;DR: The beta-substituted pyridine derivatives do not inhibit arachidonic acid cyclooxygenase or prostaglandin I2 synthetase, two other enzymes of the arachidsonic cascade.
Abstract: The enzyme thromboxane (TX) synthetase is inhibited by pyridine. The beta-substituted pyridine derivatives showed higher inhibitory potency than the gamma-substituted ones having the same side chain. Among the beta-substituted derivatives containing the omega-carboxyalkyl group, the compounds with 6-8 carbon atoms in the side chain were especially effective. The derivatives holding the phenylene group in the side chain exhibited much higher inhibitory activity than those of the alkylene type. Among them, (E)-3-[4-(3-pyridylmethyl)phenyl]-2-methylacrylic acid hydrochloride (5a) had the highest potency (IC50 = 3 x 10(-9) M). The beta-substituted pyridine derivatives and 1-substituted imidazole derivatives which had the same side chain showed almost the same potency. The beta-substituted pyridine derivatives do not inhibit arachidonic acid cyclooxygenase or prostaglandin I2 synthetase, two other enzymes of the arachidonic cascade.
TL;DR: A series of poly(n-alkyl itaconic acid esters) with side chain lengths from 7 to 20 carbon atoms have been prepared and two glass transition temperatures have been detected as discussed by the authors.
TL;DR: Modifications of the side chain, the phenolic moiety, and structures that lack the benzopyran functionality present in THC and HHC are examined, resulting in a unique family of benzoquinolines with potent analgetic activity.
Abstract: Based on the hypothesis that analgetic activity is a dissociable feature of the cannabinoid molecule, we examined modifications of the side chain, the phenolic moiety, and, most significantly, structures that lack the benzopyran functionality present in THC and (--)-9-nor-9 beta-hydroxyhexahydrocannabinol (HHC). A new grouping, the 1-methyl-4-phenylbutyloxy C-3 side chain, elaborates a unique lipopholic region. Replacement of the phenol substituent produced several derivatives which retain analgetic activity in the codeine potency range. Introduction of a weakly basic nitrogen at C-5 and deletion of the axial methyl group in the B ring, two structural changes forbidden by traditional cannabinoid SAR, resulted in a unique family of benzoquinolines with potent analgetic activity. The prototype of this series, levonantradol, exhibits potent and stereospecific analgetic and antiemetic activity.
TL;DR: Partial molar volumes of α-aminocarboxylic acids in water at 25°C were measured in this paper. But the results indicated that 4.33 ± 0.39 water molecules hydrate an α-amino acid.
Abstract: Partial molar volumes of a number of α-aminocarboxylic acids in water at 25°C are measured. The results indicate that 4.33 ± 0.39 water molecules hydrate an α-amino acid. Contributions of the side chains or their constituent parts to the partial molar volumes are deduced. Volumes of proton ionization for α-amino acids with nitrogen-containing side chains are calculated and they indicate the absence of any significant electrostatic effects by terminal charged groups.
TL;DR: The results strongly suggest that it should now be possible to observe in great detail the motions of any type of amino acid side chain in membrane proteins, including the effects of lipid composition on protein dynamics.
TL;DR: In this paper, the properties of a side chain polymer exhibiting a liquid crystalline phase in addition to a partially crystalline state and the isotropic fluid state were investigated, and the kinetics of phase transitions between these states were analyzed.
Abstract: The structures, textures as well as thermodynamic properties of a side chain polymer exhibiting a liquid crystalline phase in addition to a partially crystalline state and the isotropic fluid state were investigated. Furthermore the kinetics of phase transitions between these states were analyzed. It was found that the properties of this polymer are intermediate between that of low molecular weight liquid crystals and common polymers. In particular it was observed that the relation between the liquid crystalline texture and the structure is different from that of low molecular weight liquid crystals and that the properties of the crystalline and liquid crystalline state depend strongly on the tacticity of the polymer.
TL;DR: In this article, the effects of hydroxyl substitution in the ring D/side chain part of the molecules were studied and the shift of the heavily functionalized A/B ring system can serve as a fingerprint for different substitution patterns.
Abstract: The 13C NMR spectra of 29 highly oxygenated C, steroids with the withanolide skeleton, 24 of which are naturally occurring substances or acetates thereof, were recorded and the carbon signals fully assigned. The shifts of the heavily functionalized A/B ring system can serve as a ‘fingerprint’ for the different substitution patterns. A study of the effects of hydroxyl substitution in the ring D/side chain part of the molecules leads to conformational information, including preferred rotamers around the 17—20 and 20—22 bonds. Systems with both 17α- and 17β-oriented side chains are thus analysed.
TL;DR: In this article, the molecular structure of (Z)-N-acetyldehydrophenylalanine (1-phenyl-2,acetylaminoprop-2-enoic acid) has been determined from three-dimensional X-ray data.
TL;DR: The trimethylsilyl ethers of the epimeric pairs of sterols with saturated side chains and a pair with two double bonds in the side chain were completely separated from each other by GLC.
Abstract: Paris of C-24 epimeric sterols have been very difficult to separate by physical emthods. We report here the partial or complete separation of the trimethylsilyl ethers of nine pairs of C-24 epimeric sterols by gas liquid chromatography on a glass capillary column coated with SP-2340. The trimethylsilyl ethers of the epimeric pairs of sterols with saturated side chains and a pair with two double bonds in the side chain were completely separated from each other by GLC. The epimeric pairs with a double bond at C-22 showed partial separation. The 24β-epimer with a saturated side chain eluted before the corresponding 24α-epimer. This order was reversed for pairs of C-24 epimeric sterol trimethylsilyl ethers containing a double bond in the side chain at C-22.
TL;DR: The results indicate that a deprotonated amine is necessary for hydroxylation and that the amine may be present in the original drug rather than an external nucleophile, and the redox properties of several different phenothiazines are presented.
Abstract: The cation radical of each of the phenothiazine tranquilizers is a likely intermediate in the metabolism of the drugs to at least two of the three major metabolic classes, the sulfoxides and the hydroxylated derivatives. Previous work has shown that the reactions of the radical are highly dependent on the environment, particularly the presence of nucleophiles. The present report discusses the effect of cation radical structure on the formation of sulfoxide and hydroxylated metabolites in vitro. Cyclic voltammetry, spectrophotometry, and liquid chromatography were used to examine reactions of various phenothiazine radicals in aqueous buffers. A radical with a three-carbon aliphatic side chain (e.g., chlorpromazine) forms solely sulfoxide and parent unless amine nucleophiles are present, in which case hydroxylation occurs. A shorter side chain (e.g., promethazine) causes radical dimerization and pronounced hydroxylation, regardless of external nucleophiles. A piperazine side chain (e.g., fluphenazine) promotes hydroxylation, with some sulfoxide observed. The results indicate that a deprotonated amine is necessary for hydroxylation and that the amine may be present in the original drug rather than an external nucleophile. In addition to information about cation radical reactions, the redox properties of several different phenothiazines are presented.
TL;DR: The polyol-induced stabilization of proteins is a result of a complicated enthalpy-entropy compensation phenomenon closely related to the solvent ordering around the solute molecules; consequently, the polyol effects on nonpolar side chains do not necessarily dominate those on peptide groups in an enthalpic sense.
Abstract: The enthalpies of transfer of several amino acids and diglycine from water to aqueous polyols (glycerol, xylitol, sorbitol, and inositol) have been calorimetrically determined in order to clarify the mechanism of polyol-induced stabilization of proteins. The obtained enthalpy data were combined with the data on free energy of transfer previously determined to calculate the corresponding entropy of transfer. The enthalpies of transfer of nonpolar side chains of amino acids and peptide group were positive and negative, respectively, depending on the polyol concentration and hydrophobicity of the side chains. This indicates that the non-spontaneous transfer of nonpolar side chains to aqueous polyols is due to an enthalpy effect while that of peptide group is due to an entropy effect. These thermodynamic data are discussed in terms of changes in water structure or solvent ordering around the solute molecules. It was found that the polyol-induced stabilization of proteins is a result of a complicated enthalpy-entropy compensation phenomenon closely related to the solvent ordering around the solute molecules; consequently, the polyol effects on nonpolar side chains do not necessarily dominate those on peptide groups in an enthalpic sense.
TL;DR: It is established that replacement of Gln by Ala is without effect on backbone conformation, and a major role for the Gln side chain in peptide association is suggested by differences in the NMR behavior of the GlN(1) and Ala(1), which shows evidence for intermolecular interactions.
Abstract: 270-MHz 1H NMR studies of the 11-21 suzukacillin fragment Boc-Gln-Aib-Leu-Aib-Gly-Leu-Aib-Val-Aib-Aib-OMe (11-G) and its analogue Boc-Ala-Aib-Leu-Aib-Gly-Leu-Aib-Pro-Val-Aib-Aib-OMe (11-A) have been carried out in $CD{Cl}_3$ and ${({CD}_3)}_2SO$. The NH chemical shifts and their temperature coefficients have been measured as a function of peptide concentration in both solvents. It is established that replacement of Gln by Ala is without effect on backbone conformation. Both peptides adopt highly folded $3_{10}$ helical conformations stabilized by seven intramolecular 4 \rightarrow 1 hydrogen bonds. Nonlinear temperature dependences are demonstrated for free NH groups in the Gln(1) peptide. Aggregation is mediated by intermolecular hydrogen bonds formed by solvent-exposed NH groups. A major role for the Gln side chain in peptide association is suggested by differences in the NMR behavior of the Gln(1) and Ala(1) peptides. For the Gln(1) peptide in $CD{Cl}_3$, the carboxamide side chain carbonyl group forms an intramolecular hydrogen bond to the peptide backbone, while the trans side chain NH shows evidence for intermolecular interactions. In ${({CD}_3)}_2SO$, the cis carboxamide NH is involved in intermolecular hydrogen bonding. The possible role of the central Gln residue in sta-bilizing aggregates of peptide channel formers is discussed, and a model for hexameric association is postulated.
TL;DR: In this article, N-Oligoethylene glycol monoaza crown ethers were prepared and the notable effect of oxyethylene oxygen atoms of the side chain on complexing ability with sodium and potassium cations was confirmed.
TL;DR: For studies on the possible involvement of hydrogen bonding in base recognition from the outside of the nucleic acid double helix, 2-methoxy-6-chloro-9-aminoacridine derivatives bearing a carboxamide side chain were examined by 1H NMR spectroscopy and demonstrated a relative pyrimidine-(3'-5')-purine sequence specificity.
Abstract: For studies on the possible involvement of hydrogen bonding in base recognition from the outside of the nucleic acid double helix, 2-methoxy-6-chloro-9-aminoacridine derivatives bearing a carboxamide side chain were examined by 1H NMR spectroscopy. The study of the interaction of these derivatives with CpG or GpC demonstrated that (i) the 2-methoxy-6-chloro-9-aminoacridine ring intercalates preferentially in the minihelix formed by CpG, which indicates a relative pyrimidine-(3'-5')-purine sequence specificity that contrasts with the simple 9-aminoacridine ring wherein Reuben et al. [Reuben, J., Baker, B. M., & Kallenbach, N. R. (1978) Biochemistry 17, 2916-2919] did not observe any sequence preference (ii) the geometry of the intercalated minihelical complex of the 2-methoxy-6-chloro-9-[(5-carbamolypentyl)-amino]acridine with CpG as deduced from isoshielding curves resembles that found in the crystalline complexes of proflavin, with several autocomplementary dinucleoside monophosphates, (iii) the terminal carboxamide group borne by the side chain of 2-methoxy-6-chloro-9-[(5-carbamoylpentyl)amino]acridine (5) intercalated in CpG lies in the small groove and seems to interact through hydrogen bonds with the adjacent guanine.
TL;DR: N(α)-t-Butoxycarbonyl-N(π)-4-bromo-benzyloxymethyl-L-histidine derivatives for peptide synthesis with histidine have been shown to have convenient, physical properties, no side reactions were encountered, and the final deprotection proceeded smoothly as discussed by the authors.
Abstract: N(α)-t-Butoxycarbonyl-N(π)-benzyloxymethyl-L-histidine (1) and N(α)-t-butoxycarbonyl-N(π)-4-bromo-benzyloxymethyl-L-histidine (2) have been prepared and shown to be suitable derivatives for peptide synthesis with histidine; the synthetic intermediates had convenient, physical properties, no side reactions were encountered, and the final deprotection proceeded smoothly under mild conditions.
Patent•
12 Oct 1981
TL;DR: In this paper, copolymerization and cross-linking of an amide of an unsaturated carboxylic acid such as acrylamide or methacrylamides was used to produce a contact lens form and then hydrated to form a hydrogel.
Abstract: Polymeric materials suitable for biomedical applications, particularly in making contact lenses, are formed by copolymerization and crosslinking of: (1) an amide of an unsaturated carboxylic acid such as acrylamide or methacrylamide; (2) an N-vinyl lactam such as N-vinyl pyrrolidone; (3) an ester of an unsaturated carboxylic acid such as a hydroxy-substituted ester of acrylic or methacrylic acid; (4) an unsaturated carboxylic acid such as acrylic or methacrylic acid; and (5) a hydrophobic monomer component comprising: (a) a fluorine-containing polymerizable monomer having a fluoroaliphatic side chain, such as fluoroalkyl acrylate or methacrylate, and (b) a non-fluorine-containing polymerizable hydrophobic vinyl monomer such as styrene; crosslinking with a crosslinking agent either being carried out during copolymerization or subsequently. The resulting polymeric materials may be machined to produce a contact lens form and then hydrated to form a hydrogel which is suitable for use as an extended wear contact lens.
TL;DR: Jasmonoids with cis-2-pentenyl side chain such as cis-jasmone, methyl jasmonate and jasmolone were easily synthesized from cis-4-heptenoic acid obtained by the ring opening reaction of β-propiolactone with di-cis-butenylcuprate as mentioned in this paper.
Abstract: Jasmonoids with cis-2-pentenyl side chain such as cis-jasmone, methyl jasmonate, and jasmolone were easily synthesized from cis-4-heptenoic acid obtained by the ring opening reaction of β-propiolactone with di-cis-butenylcuprate.