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PubMed1984

Concurrent measurements of blood flow and transcapillary transport in avian sarcoma virus-induced experimental brain tumors: implications for chemotherapy.

A blood-to-tissue transfer constant, K, and tissue blood flow, F, were measured concurrently in seven rats with a total of 19 separate brain tumors induced by intracerebral inoculation of avian sarcoma virus. Regional and local measurements of K and F were obtained using double-label quantitative autoradiography with alpha-[14C]aminoisobutyric acid and [131I]iodoantipyrine, computerized microdensitometry and image analysis. Apparent tissue extraction fractions and capillary permeability-surface area products were calculated for different tumor regions, brain adjacent to tumor and tumor-free brain. The following observations were made: five histological categories of the tumors were found; significant local and regional variations of both K and F were typical in each group, resulting in marked regional variability of permeability-surface area products but more uniform values of apparent extraction fraction; the values of F, K, permeability-surface area products and apparent extraction fraction correlated poorly with morphological features of the tumors (necrosis, cellularity, cytology, location and size); the extraction fraction of alpha-aminoisobutyric acid was usually highest in tumor centers and then decreased in a gradient from tumor periphery through adjacent brain; and regardless of classification or histological features, capillary permeability and surface area, and not tissue perfusion or blood flow, seem to determine the blood-to-tissue transport processes (delivery of bloodborne materials) in most regions of these experimental brain tumors. An operational pharmacokinetic model of drug concentration in tumor tissue is developed and the results of our analysis indicate that increases in capillary permeability such as measured in these studies would not be sufficient to deliver adequate amounts of water-soluble drugs with short plasma half-lives to tumor tissue.

Animals↗
PubMed1995

Immediate cerebrovascular responses to closed head injury in the rat.

Changes in cerebrovascular dynamics were investigated immediately after closed head injury in the rat using a newly developed closed head injury model developed by Marmarou et al. Intracranial pressure (ICP) and mean arterial blood pressure (MABP) were monitored before and after trauma. Regional cerebral blood flow (rCBF), regional cerebral plasma volume (rCPV), and blood-brain barrier (BBB) permeability were measured autoradiographically with iodo[14C]antipyrine [14C]sucrose, and [alpha-14C]aminoisobutyric acid, respectively. rCBF responses to induced hypertension after trauma were measured by laser-Doppler flowmetry to investigate the status of autoregulation. Before injury, baseline ICP values ranged from 6 to 10 mm Hg in all animals. Immediately after trauma, ICP increased synchronously with MABP to > 100 mm Hg and then rapidly returned to baseline values: MABP increased rapidly by 20% after trauma and returned to baseline values within 30 sec. At 30 sec after injury, a significant increase in rCBF was observed in five subcortical regions (p < 0.05), and a significant increase in rCPV was observed in the frontal cortex, parietal cortex, thalamus, and hypothalamus (p < 0.05). At 10 min after injury, BBB permeability (the transfer constant for [alpha 14C]aminoisobutyric acid) was < 0.1 mL/kg/min for all regions except those with a relatively permeable BBB, for example, median eminence, choroidal plexus, pineal body, and pituitary gland. Induced hypertension resulted in a prolonged increase in rCBF after trauma. Thus, in this closed head injury model, which is not associated with marked hypertension or prolonged BBB disruption, widespread increases in rCBF and impaired cerebral autoregulation were apparent immediately after injury.

Animals↗
PubMed1985

L-Triiodothyronine (T3) stimulates growth of cultured GC cells by action early in the G1 period: evidence for mediation by the nuclear T3 receptor.

Incubation with T3 results in a dose-dependent increase in growth rate of cultured GC cells, a GH-producing rat pituitary tumor cell line. The T3-induced increase in growth rate results mainly from shortening of the G1 period from 79.4 +/- 4.3 (SD) h in cells grown in T3-depleted medium (-T3) to 10.0 +/- 0.9 h. This effect can also be demonstrated in synchronized populations. Addition of T3 (0.3 nM) to cells synchronized in early G1 in the absence of T3 shortened the G1 period, estimated from graphic data, from more than 40-50 h to 13.4 +/- 2.1 h (n = 7). To determine the mechanism of this T3 effect, GC cells were grown in Dulbecco's modified Eagle's medium containing 10% serum plus or minus T3 (0.3 nM) and synchronized at the beginning of the G1 period by mitotic selection. Mitotic cells (85-100%), obtained by controlled mechanical shaking, were isolated by centrifugation and replated. The end of G1 was determined by the onset of DNA synthesis with [3H]thymidine as assessed by autoradiography (percent labeled nuclei). L-T3-induced shortening of G1 was detectable at 0.05 nM T3, half-maximal at physiological T3 (0.17 nM), and maximal between 0.3 nM and 1.0 nM T3. Addition of cycloheximide, 0.025 microgram/ml or 1.0 microgram/ml, decreased protein synthesis by 50% and 90%, respectively, and attenuated the T3 effect on G1 by 80-90%. The attenuation of the T3 effect on G1 by cycloheximide at a dose which inhibited protein synthesis suggests that T3-induced shortening of G1 may require new protein synthesis. Since glucocorticoids decrease the effect of T3 on induction of alpha-aminoisobutyric acid transport, their effect on T3-induced shortening of G1 was determined in G1-synchronized GC cells and in asynchronous cultures. Cortisol, 100 nM, significantly decreased the growth rate of asynchronous GC cells and attenuated the effect of T3 in G1-synchronized cells. Finally, T4 also decreased the length of G1 in a dose-dependent manner with a half-maximal effect at 40.0 nM. The half-maximal effect of T4 occurred at a nuclear iodothyronine concentration that was comparable to that achieved in incubations with 0.17 nM T3 (half-maximal dose). Thus, half-maximal shortening of G1 in synchronized GC cell cultures occurred at iodothyronine concentrations required for half-maximal occupancy of nuclear T3 receptors and for half-maximal induction of GH synthesis, growth rate, alpha-aminoisobutyric acid uptake, and depletion of the nuclear T3 receptor.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1981

Stretch-induced growth of skeletal myotubes correlates with activation of the sodium pump.

Skeletal myotubes responded to passive stretch by increased amino acid uptake (as measured with [3H]alpha-aminoisobutyric acid), increased incorporation of amino acids into total cellular protein and myosin heavy chains, and increased accumulation of total cellular protein and myosin heavy chains. These alterations were preceded by an increase in the uptake of ouabain-sensitive rubidium-86 (86Rb+), a potassium tracer used to measure membrane sodium pump activity (Na+K+ATPase). This stretch-induced stimulation of 86Rb+ uptake resulted from a 60-70% increase in the Vmax of the Na pump with little change in the Km. [3H] ouabain binding studies showed no stretch-induced change in the number of membrane Na pumps, indicating that stretch activates the Na pumps that are already present on the cell surface. Since the stretch-induced increases in amino acid transport and amino acid incorporation into proteins were inhibited by ouabain, Na pump activation may be involved in stretch-induced cell growth of skeletal muscle cells by hypertrophy.

Aminoisobutyric Acids↗
PubMed1991

Oleic acid reversibly opens the blood-brain barrier.

This study examined the effect of intracarotid oleic acid infusion on blood-brain barrier permeability. Oleic acid was infused for 30 s at a rate of 6 ml/min into the right internal carotid artery at concentrations of 10(-6), 10(-5), 2 x 10(-5) and 5 10(-5) M. Extensive Evans blue-albumin extravasation was observed 15 min after the administration of 2 x 10(-5) M oleic acid. The permeability surface area product for alpha-aminoisobutyric acid (AIB), determined 1-11 min following the infusion of oleic acid was increased 10-fold following infusion of 10(-5) M oleic acid and 20-fold following the administration of 5 x 10(-5) M oleate. The blood-brain barrier opening to AIB proved to be reversible 80-90 min after the infusion of 2 x 10(-5) M oleic acid. The possible mechanisms of the oleic acid effect are discussed.

Aminoisobutyric Acids↗
PubMed1981

Glucocorticoid regulation of amino acid transport in anucleate rat hepatoma (HTC) cells.

The transport of alpha-aminoisobutyric acid (AIB) by rat hepatoma tissue culture (HTC) cells is rapidly and reversibly inhibited by dexamethasone and other glucocorticoids. To investigate the role of the nucleus in the regulation of transport and to determine whether steroid hormones or steroid-receptor complexes may have direct effects on cytoplasmic or membrane functions, we have examined the regulation of transport by dexamethasone in anucleate HTC cells. Cytoplasts prepared from suspension cultures of HTC cells fully retain active transport of AIB with the same kinetic properties as intact cells. However, the uptake of AIB is not inhibited by dexamethasone or other corticosteroids. Neither is the inhibited rate of transport, manifested by cytoplasts prepared from dexamethasone-treated cells, restored to normal upon removal of the hormone. Anucleate cells exhibit specific, saturable binding of [3H]dexamethasone; however, the binding is reduced compared with that of intact cells. The nucleus is thus required for the glucocorticoid regulation of amino acid transport in HTC cells.

Aminoisobutyric Acids↗
PubMed2000

Comparison of helix-stabilizing effects of alpha,alpha-dialkyl glycines with linear and cycloalkyl side chains.

The ability of alpha, alpha-di-n-alkyl glycines with linear and cyclic alkyl side chains to stabilize helical conformations has been compared using a model heptapeptide sequence. The conformations of five synthetic heptapeptides (Boc-Val-Ala-Leu-Xxx-Val-Ala-Leu-OMe, Xxx = Ac8c, Ac7c, Aib, Dpg, and Deg, where Ac8c = 1-aminocyclooctane-1-carboxylic acid, Ac7c = 1-aminocycloheptane-1-carboxylic acid, Aib = alpha-aminoisobutyric acid, Dpg = alpha,alpha-di-n-propyl glycine, Deg = alpha,alpha-di-n-ethyl glycine) have been investigated. In crystals, helical conformations have been demonstrated by x-ray crystallography for the peptides, R-Val-Ala-Leu-Dpg-Val-Ala-Leu-OMe, (R = Boc and acetyl). Solution conformations of the five peptides have been studied by 1H-nmr. In the apolar solvent CDCl3, all five peptides favor helical conformations in which the NH groups of residues 3-7 are shielded from the solvent. Successive NiH<-->Ni + 1H nuclear Overhauser effects over the length of the sequence support a major population of continuous helical conformations. Solvent titration experiments in mixtures of CDCl3/DMSO provide evidence for solvent-dependent conformational transitions that are more pronounced for the Deg and Dpg peptides. Solvent-dependent chemical shift variations and temperature coefficients in DMSO suggest that the conformational distributions in the Deg/Dpg peptides are distinctly different from the Aib/Acnc peptides in a strongly solvating medium. Nuclear Overhauser effects provide additional evidence for the population of extended backbone conformations in the Dpg peptide, while a significant residual population of helical conformations is still detectable in the isomeric Ac7c peptide in DMSO.

Crystallography, X-Ray↗
PubMed1999

Characterization of glycine transport in cultured Müller glial cells from the retina.

Rapid termination of the synaptic action of glutamate (Glu) and glycine (Gly) is achieved by uptake into the presynaptic terminal and glial cells. In the vertebrate CNS, Gly acts both as an inhibitory neurotransmitter and as a Glu modulator or coagonist at postsynaptic N-methyl-D-aspartate (NMDA) receptors. We have previously described NMDA receptors in Müller cells of chick retina coupled to the phosphoinositide cascade, the entry of calcium, and the activation of protein kinase C (PKC; López-Colomé et al. Glia 9:127-135, 1993). A colocalization of Gly transporters and NMDA receptors has been reported in brain tissue (Smith et al. Neuron 8:927-936, 1992); since the concentration of Gly could participate in the modulation of Glu excitatory transmission in the vertical pathways of the retina, transport of Gly in monolayer cultures of Müller cells was studied. Gly transport was found pH-sensitive with an optimum at pH 7.4. Kinetic analysis of the saturation curve for Gly within a concentration range of 0.01-2 mM, revealed two components of transport: a low-affinity system with Km = 1.7 mM, Vmax = 30 nmol/10 min/mg protein, and a high-affinity one with a Km = 27 microM, Vmax = 3 nmol/10 min/mg protein. Both systems were Na+ -dependent; the high-affinity system proved also dependent on external Cl- and was inhibited by sarcosine, characteristic of GLYT1 transporters. The inhibition of low-affinity uptake by 2-(methylamino)isobutyric acid (MeAIB) and 2-aminoisobutyric acid (AIB) suggests the presence of transport system A in Müller cells. The process is energy-requiring, since Gly transport was decreased by metabolic inhibitors. Data obtained are in keeping with a modulatory role for Müller glia on excitatory transmission in the retina.

2,4-Dinitrophenol↗
PubMed2000

The first water-soluble 3(10)-helical peptides.

Two water-soluble 3(10)-helical peptides are synthesized and fully characterized for the first time. The sequence of these terminally blocked heptamers comprises two residues of the Calpha-trisubstituted alpha-amino acid 2-amino-3-[1-(1,4,7-triazacyclononyl)]propanoic acid and five residues of a Calpha-tetrasubstituted alpha-amino acid (either alpha-aminoisobutyric acid or isovaline). Using CD and NMR techniques we were able to show that both heptapeptides are well structured in water, and that the type of conformation adopted is indeed the ternary 3(10)-helix.

Journal Article↗
PubMed1991

Subregional topography of capillaries in the dorsal vagal complex of rats: II. Physiological properties.

The differentiated cytoarchitecture, neurochemistry, and capillary organization of the rat dorsal vagal complex prompted this comprehensive investigation of microvascular physiology in 11 subdivisions of area postrema, 5 subnuclei of nucleus tractus solitarii (NTS), the dorsal motor nucleus of the vagus nerve, and 4 other gray matter structures in the dorsal medulla oblongata. Microvascular exchangeable volume (residual plasma volume), capillary blood and plasma flow, and unidirectional transfer constants for a tracer amino acid, [14C]alpha-aminoisobutyric acid (AIB), varied considerably among the structures analyzed. Exchangeable volume, largest in area postrema medial zones (about 29 microliters.g-1) and smallest in medullary gray matter (7-11 microliters.g-1), correlated directly with subregional densities of capillaries and rates of tissue glucose metabolism. Capillary blood flow (range of 1,430-2,147 microliters.g-1.min-1), plasma flow, and tissue glucose metabolism (range of 0.48-0.71 mumol.g-1.min-1) were linearly related in the dorsal vagal complex. The most striking quantitative difference among structures in this brain region were the rates of transcapillary influx and derived permeability X surface area (PS) products of [14C]AIB, which has physicochemical properties resembling those of hormones. PS products for AIB were negligible in most medullary gray matter regions (less than 1 microliter.g-1.min-1, indicative of blood-brain barrier properties), but were 20-59X and 99-402X higher in NTS subnuclei and area postrema, respectively. An extraordinary feature of the microcirculation in area postrema was the long-duration transit of tracer sucrose and blood, a characteristic that would amplify the sensing ability of area postrema as it monitors the composition of the circulation.

Animals↗
PubMed2000

Collateral existence of folded and extended conformations of the beta-Ala moiety in a model peptide.

The single-crystal X-ray diffraction analysis of a nonchiral beta-Ala-containing model peptide, Boc-beta-Ala-Aib-OCH(3) 1 (beta-Ala, 3-aminopropionic acid; Aib, alpha-aminoisobutyric acid), establishes the coexistence of distinctly different backbone conformations in two crystallographically independent molecules, A and B, in the asymmetric unit. Interestingly, the central mu torsion angle around the -C(beta)-C(alpha)- bond of the conformationally flexible beta-Ala residue appears to be critical in dictating the overall distinct structural features, i.e., in molecule A it adopts a folded gauche conformation: mu = -71.0 degrees, whereas it favors an extended trans conformation, mu = 161.2 degrees, in molecule B. As expected, the stereochemically constrained Aib residue preferred an energetically favorable folded backbone conformation, the torsion angles being phi = 46.2 degrees and psi = 48.3 degrees for molecule A and phi = -43.6 degrees and psi = -45.5 degrees for molecule B, lying in the left-handed and right-handed helical regions of the Ramachandran map, respectively. Considering the signs as well as the magnitudes of the backbone torsional angles, molecule A typically folds into a pseudo type III' beta-turn-like structure while molecule B prefers an overall extended conformation. Entrapping the two dramatically distinct conformational characteristics in the crystalline state clearly suggests that the gauche and the trans effects of the beta-Ala moieties are indeed energetically accessible to a short linear peptide and receive strong experimental support. The analyses permitted us to emphasize that in addition to conformational constraints of the neighboring residue, the chemical nature of the side-chain acyclic substituents and the "local environments" collectively seem to influence the stabilization of the folding-unfolding behavior of the two methylene units (-CONH-CH(2)-CH(2)-CONH-) in 1.

Crystallography, X-Ray↗
PubMed2006

Peptaibiomics: an advanced, rapid and selective analysis of peptaibiotics/peptaibols by SPE/LC-ES-MS.

"Proteomics" and "peptidomics" are used as technical terms to define the analysis and study of all proteins and peptides expressed in an organism or tissue. In analogy we propose the name peptaibiomics for the analysis of a group of fungal peptide antibiotics (peptaibiotics) containing the characteristic amino acid Aib (alpha-aminoisobutyric acid). In analogy to the peptidome the complete expression of peptaibiotics by fungal multienzyme complexes should be named the peptaibiome. Peptaibiotics are defined as peptides containing Aib and exerting a variety of bioactivities. They comprise the sub-groups of N-acetylated peptaibols, characterized also by a C-terminal amide-linked 2-amino alcohol, and lipopeptaibols having in place of an acetyl group a lipophilic fatty acid acyl group. Furthermore, lipoaminopeptides are also known with long-chain fatty acid on the N-termini, a lipoamino acid in position three and a strongly basic secondary or tertiary amine form a subgroup of mixed forms which could not be integrated in one of these three previously mentioned groups. Here we present a specific and rapid screening method on the peptaibiome applicable directly onto filamentous fungi cultured in a single Petri dish. The method comprises solid-phase extraction (SPE) of peptaibiotics followed by on-line reversed-phase HPLC coupled to an ion trap electrospray tandem mass spectrometer (ES-MS). The presence of these peptides is indicated by characteristic mass differences of Deltam = 85.1 Da representing Aib-residues which can be observed in the b-series of acylium fragment ions resulting from ES-MS. Partial sequences can be deduced from the data and compared with structures compiled in electronic peptaibol data bases. The judgement is possible whether or not structures are novel, already known or related to known structures. Suitability of the method is demonstrated with the analysis of strains of Trichoderma and its teleomorph Hypocrea. New sequences of peptaibiotics are presented and those being related to established 10- to 18-residue peptaibols trichovirin, trichogin and trichotoxin, which have been described in the literature.

Anti-Bacterial Agents↗
PubMed1979

Increased sodium ion influx is necessary to initiate rat hepatocyte proliferation.

Serum-free media containing 10-50 ng insulin, glucagon and epidermal growth factor (EGF) ml-1 stimulate adult rat hepatocyte proliferation in 10-15 day old primary liver cell cultures. The kinetics of this response simulate hepatocellular transitions that accompnay liver regeneration after 67% hepatectomy. Amiloride, a Na+ influx inhibitor, reversibly blocks these transitions in vitro (ID50 approximately 0.02 mM) and in vivo (ID50 approximately 25 mg kg-1). Inhibition is observed with other cation flux modulators, including ouabain (ID50 approximately 0.2 mM), 0.2 microM monensin and 0.2 microM nigericin, but not with 0.3 mM furosemide or tetrodotoxin. The prereplicative interval in culture (0-12 hr) is characterized by preferential cellular responsiveness to EGF (0-3 hr) followed by insulin plus glucagon (3-12 hr). Parallel culture and animal studies show that the amiloride-sensitive and prereplicative intervals coincide. In culture, a "burst" of 22Na+ influx, stimulated by peptide-supplemented media within 1 min but decreased later at 12 hr, is retarded by amiloride. This drug also blocks delayed prereplicative events involving increased amino acid "A" transport system function at 4-8 hr, and 3H-uridine and 3H-leucine incorporation into RNA and protein, respectively, at 8-12 hr. These findings suggest that at least two time-ordered processes are necessary to initiate hepatic growth fully: first, activation of Na+ flux systems by peptides similar or identical to EGF; and second, potentiation of these and subsequent cellular events by the combined action of insulin plus glucagon. [Amiloride: N-amidino-3,5-diamino-6-chloropyrazinecarboxamide; furosemide: 4-chloro-N-furfuryl-5-sulfamoylanthranilic acid; AIB: alpha-aminoisobutyric acid; ID50: administered dose giving 50% inhibition of a maximal response; dFBS: dialyzed fetal bovine serum; L.I.: 3H-dT nuclear labeling index.]

Amiloride↗
PubMed1994

Hyper-stimulation of monoclonal antibody production by high osmolarity stress in eRDF medium.

An earlier study (Chua et al., 1994) showed that hybridoma 2HG11 cultivated in a basal medium called eRDF, which is enriched in amino acids, enabled higher immunoglobulin (Ig) production with and without serum, when compared to two other traditional media RPMI and DMEM/F12. A further enhancement of Ig productivity was achieved when the osmolarity of the culture medium was increased from 300 mOsm to 350 mOsm (Oh et al., 1993). To determine whether the eRDF media was indeed better, three other cell lines, two IgG producers (TB/C3 and I13/17) and an IgM producer (B10), were tested. The results showed that maximum viable cell densities in eRDF medium were up to 3-times higher than in RPMI and maximum Ig titres were 2-8-times higher than in DMEM/F12 and RPMI. The three cell lines were similarly subjected to osmotic increases from 300 mOsm to 350 and 400 mOsm by addition of NaCl. There was an increase in Ig titres of between 30% to 100% compared to the control medium, although cell growth was reduced. Thus, hyper-stimulation by osmolarity stress was found to be generally effective in eliciting higher Ig production; the extent of enhancement being more pronounced for certain cell lines. Other osmolytes such as sucrose and KCl demonstrated similar effects of increasing Ig productivity. Study on the mechanism of action of osmotic stress on hybridoma 2HG11 revealed that hyper-stimulation of Ig productivity was fundamentally related to a greater availability of amino acids to cells as the cells actively accumulated more salt and amino acids to compensate for the higher medium osmolarity. Uptake of the amino acid analogues 14C-aminoisobutyric acid and 3H-methylaminoisobutyric acid into cells increased to 2.34 x 10(3) cpm per cell per min and 6.35 x 10(3) cpm per cell per min, respectively, under osmotic stress. This corresponds to an 85% increase in uptake via the Na(+)-dependent symport and a 50% increase in uptake via the Na(+)-independent and Na(+)-dependent symports. In the 350 mOsm medium, hybridomas also demonstrated an increase in metabolic activities of 5-10% compared to the control. This, together with the reduced specific growth rate in cells under osmotic stress, suggests that more energy was channelled into the biosynthetic pathway of Ig production.

Amino Acids↗
PubMed1994

High performance liquid chromatography of carbon-11 labeled thymidine and its major catabolites for clinical PET studies.

The identity and pharmacology of the rapidly formed radiolabeled metabolites formed following i.v. injection of C-11 thymidine (TdR) labeled in the 5-methyl-position are being studied in animal models and patients with cancer. A high performance liquid chromatographic (HPLC) procedure has been developed for the separation of these metabolites including thymine, dihydrothymine, beta-ureidoisobutyric acid, and beta-aminoisobutyric acid from plasma and tissue extracts. Information obtained regarding the pharmacokinetics of the metabolites are being used to generate mathematical models for C-11 TdR incorporation rates into DNA.

Animals↗
PubMed1997

Modification of amino acids at shock pressures of 3.5 to 32 GPa.

Amino acids were subjected to shock impact over a pressure range of 3.5 to 32 GPa both within and without meteoritic mineral matrices. The extent of amino acid destruction, racemization, and conversion to secondary amino acids was examined. Abundances of parent compounds decreased by a factor of 10(3) over this pressure range. Racemization also occurred, but some residual optical activity remained in the amino acids surviving shocks up to 32 GPa. Secondary amino acids formed in the high peak pressure range; those identified were beta-alanine, glycine, alanine, gamma-aminobutyric acid, and beta-aminoisobutyric acid. At 30 GPa, the abundances of these daughter compounds exceeded those of the remaining initial amino acids. As the concomitant effects of high mechanical stress and temperature accompanying shocks cannot be separated in this work, their relative contribution to the observed transformations cannot be estimated. The survival of amino acids in shock experiments suggests that, after formation or emplacement of amino acids in carbonaceous chondrite parent bodies, these objects never experienced impact velocities greater than 5 km/s, which suffices to generate 30 GPa for typical silicate/silicate impacts. These results also provide guidelines for choosing appropriate capture media for interplanetary dust particles on Earth-orbiting platforms.

Aluminum↗
PubMed2000

Entrapping unusual folding characteristics of the beta-Ala residues in a model peptide: Boc-beta-Ala-Aib-beta-Ala-NHCH3.

Crystal structure analysis of a model peptide: Boc-beta-Ala-Aib-beta-Ala-NHCH3 (beta-Ala: 3-amino propionic acid; Aib: alpha-aminoisobutyric acid) revealed distinct conformational preferences for folded [phi approximately 136 degrees, mu approximately -62 degrees, psi approximately 100 degrees] and semifolded [phi approximately 83 degrees, mu approximately -177 degrees, psi approximately -117 degrees] structures of the N-and C-terminus beta-Ala residues, respectively. The overall folded conformation is stabilized by unusual Ni...H-Ni+1 and nonconventional C-H...O intramolecular hydrogen bonding interactions.

Hydrogen Bonding↗
PubMed1980

A colchicine-sensitive uptake system in Morris hepatomas.

The interference of microtubular disruptors with the uptake of amino acids and other low molecular weight substrates has been studied in Morris hepatomas, host liver, and regenerating liver. Colchicine inhibits amino acid transport (alpha-aminoisobutyric acid, L-methionine, and L-leucine) in hepatomas by 59-98% whereas transport in host and regenerating liver is not impeded but increased. In hepatomas, treatment urea, and carbonate. Vinblastine, but not lumicolchicine or cytochalasin B, is an effective inhibitor. The inhibition of uptake is not linked to a decrease of cellular ATP and UTP. The data suggest that the transport of low molecular weight substrates in hepatomas is related to microtubules or other colchicine-binding structures, e.g., of the plasma membrane. This colchicine-sensitive uptake system in hepatomas may be due to the malignant transformation of hepatocytes.

Amino Acids↗