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Biomedical subjects

J T Yang

Publications and source records attributed to J T Yang.

At least 91 records · Page 5Linked to original sources
PubMed1981

Sequence-dependent conformations of short polypeptides in a hydrophobic environment.

Surfactants, which provide a hydrophobic environment, may induce an ordered conformation in polypeptides and proteins that contain a sequence with helix-or beta-forming potential. This hypothesis has been illustrated in circular dichroic studies of oligopeptides and short polypeptides. These peptide-surfactant complexes can form (1) a helix, (2) a beta-form, (3) either form (depending on experimental conditions), or can remain in (4) an ordered form. The induced helix is stable in a surfactant solution below or above its critical micellar concentration, whereas the induced beta-form is usually converted back to an unordered form when the surfactant used is above its critical micellar concentration, or it is transformed into a helix in excess surfactant solution if the peptide has both the helix- and beta-forming potential. In most cases the observed conformations agree with those predicted from the amino acid sequences of the peptides. The induced conformation of a peptide can be destabilized by charges on the side groups having the same sign as that of surfactant ions. Disulfide bonds can inhibit the formation of induced conformation because of steric hindrance. The terminal effect can prevent a peptide from forming an ordered conformation near the NH2- and COOH-terminus.

Amino Acid Sequence↗
PubMed1981

Conformation of insulin and its fragments in surfactant solutions.

The conformation of insulin, A and B chains and des(B23-30)octapeptide insulin (DOI) in surfactant solutions was studied by circular dichroism (CD). Addition of sodium dodecyl sulfate (NaDodSO4), dodecylammonium chloride (DodNH3Cl) or dodecyltrimethylammonium chloride (Dod(CH3)3NCl) slightly alters the CD spectrum of insulin, but not DOI. The CD of insulin in NaDodSO4 solution resembles that of DOI without the surfactant, suggesting the dissociation of the COOH-terminal antiparallel beta-form of insulin oligomers (DOI lacks B23-30 and exists as monomers). Reduced insulin and DOI lose their ordered structure in water, but their helical conformation is restored in surfactant solutions. Reduced DOI in NaDodSO4 solution appears to be more helical than DOI with the disulfide bonds intact as judged from their ellipticities. Oxidized A and B chains of insulin are unordered in aqueous solution. A chain that lacks cationic side groups remains unordered in a NaDodSO4 solution. It shows a small amount of helix in a Dod(CH3)3NCl solution and forms the interchain beta-form in a DodNH3Cl solution. In contrast, B chain becomes partially helical in all three surfactant solutions.

Animals↗
PubMed1981

Ordered conformation of polypeptides and proteins in acidic dodecyl sulfate solution.

The conformation of some polypeptides and proteins in sodium dodecyl sulfate (NaDodSO4) solutions was studied by circular dichroism. The type and extent of induced structure depend on their helix- and beta-forming potential. Anionic side groups in segments of helix or beta form tend to destabilize the ordered structure unless they are protonated. beta-Endorphin has one Glu inside a predicted helical segment; its helicity in a NaDodSO4 solution is enhanced at pH below 4. alpha-Melanocyte-stimulating hormone having a Glu in a beta segment undergoes a pH-induced coil to beta transition in 1.25 mM NaDodSO4 (excess surfactant will disrupt the beta form). Reduced somatostatin assumes a beta form in 2 mM NaDodSO4 and a partial helix in 25 mM NaDodSO4, both of which are unchanged in acidic pH because it lacks -COOH groups. The unordered gastrin with five consecutive Glu's becomes helical in a NaDodSO4 solution at pH 4. Neurotensin with one Glu has no structure-forming potential and is unordered in both neutral and acidic NaDodSO4 solutions. This charge effect also manifests in segments of ordered structure for polypeptides and proteins such as glucagon, cytochrome c, parvalbumin, ribonuclease A, and lysozyme. The effect is especially predominant in tropomyosin that is rich in clusters of anionic side groups. Its more than 90% helicity is reduced to about one-half in a neutral NaDodSO4 solution, but most of it can be restored by lowering the pH to 2.4.

Animals↗
PubMed1981

Biotransformation of reproterol in the intestinal tract of the rat.

The major metabolite of reproterol (Broncho-spasmin) in rat feces is 2-[3-theophyllinyl(7)-propyl]-4,6,8-trihydroxy-1,2,3,4-tetrahydroisoquinoline. It was also found in the bile of orally or intravenously dosed rats in the form of glucuronides. The biotransformation of an oral dose of reproterol to this metabolite occurred mostly in the cecum-colon section of the intestinal tract. Experiments in antibiotic treated rats showed no significant effect of the treatment on the extent of metabolite formation. This metabolite was also formed by incubation of reproterol with cecum-colon homogenates under aerobic as well as anaerobic conditions. The pharmacological action after an oral dose must be attributed to reproterol absorbed as intact form, since the metabolite is inactive.

Animals↗
PubMed1980

Ordered conformations of cationic polypeptides in anionic surfactant solutions.

Ionic poly(L-ornithine) at 45 degrees adopts a helical conformation in the presence of sodium dodecyl sulfonate or phosphate just as it is in sodium dodecyl sulfate solution as evidenced from circular dichroic spectra. But the polypeptide remains unordered in sodium tridecanate. Under similar conditions ionic poly(L-lysine) assumes the beta-form in all four anionic surfactant solutions. In sodium dodecyl phosphate solution at 45 degrees (Lys)n also undergoes a beta-to-helix transition in alkaline solution with a midpoint at pH 9.2, noting that dodecyl phosphoric acid has two dissociation constants with pKa of about 3 and 8. Raising the pH of the solution above 11 at 45 degrees converts the helical conformation back to the beta-form. This contrasts with a single beta-to-helix transition at pH 10.9 at 45 degrees for (Lys)n in sodium dodecyl sulfate solution.

Anions↗
PubMed1980

Do amino acids reverse the sickling of erythrocytes containing hemoglobin S?

Homoserine, asparagine and glutamine do not restore the deformability of deoxygenated sickle cells in spite of noticeable morphological changes. These amino acids also do not raise the minimum gelling concentration of deoxyhemoglobin S. The use of these compounds as anti-sickling agents is therefore doubtful.

Amino Acids↗
PubMed1979

beta-Endorphin: formation of alpha-helix in lipid solutions.

Human beta-endorphin adopts a partial helical conformation in aqueous solutions of cerebroside sulfate, ganglioside GM1, phosphatidylserine, and phosphatidic acid, but not of cerebroside and phosphatidylcholine, as evidenced by circular dichroic spectra. Addition of Ca2+ to the peptide in cerebroside sulfate solution can break up the helix; at 10 mM Ca2+ the peptide (12 microM) essentially exists in an unordered form. For comparison, sheep beta-lipotropin in acidic cerebroside sulfate solution (pH less than 4) also has a partial helical conformation of the complex between human beta-endorphin and lipids may be related to the opiatelike function of this peptide hormone.

Adrenocorticotropic Hormone↗
PubMed1979

Induced helical conformation of ionic polypeptides by phospholipids solubilized in a nonionic surfactant solution.

Phosphatidylcholine that has been solubilized in hexadecylpoly (oxyethylene) ether can induce a coil-to-helix transformation for poly (L-glutamic acid) in neutral solution. Similarly, solubilized phosphatidylserine promotes a helical conformation of poly (L-lysine) at neutral pH through complex formation. The mixed micelles of a phospholipid and a nonionic surfactant are thermodynamically stable and do not separate on standing. The nonionic surfactant here has no effect on the conformation of the two polypeptides.

Amino Acids↗
PubMed1979

Metabolites of 2-(3-trifluoromethylphenyl)tetrahydro-1,4-oxazine (CERM) 1841) in rats and dogs.

1. In rats and dogs dosed with 14C-labelled 2-(3-trifluoromethylphenyl)tetrahydro-1,4-oxazine hydrochloride, the 14C was excreted in the urine. The 14C eliminated in the faeces of dog was significantly higher than for rat. 2. Conjugated metabolites, mostly glucuronides, accounted for the greater part of the urinary radioactivity in both species. 3. Biotransformation products were predominantly acids in both species, followed by significant amounts of basic metabolites, with very little neutral substances. 4. The major urinary metabolite in rats was 3-trifluoromethylbenzoic acid and 3-trifluoromethylhipuric acid. In the dog it was 3-trifluoromethylmandelic acid in addition to the benzoic acid and its conjugate. The basic products identified in the urine of both species were unchanged drug and 1-amino-2-hydroxy-2-(3-trifluoromethylphenyl)ethane, with the first predominating.

Administration, Oral↗
PubMed1978

Circular dichroic analysis of protein conformation: inclusion of the beta-turns.

The mean residue ellipticity, [theta], at any wavelength, lambda, of a protein in aqueous solution is expressed as [theta]lambda = fH[theta]H infinity(1-k/n) + f beta[theta]beta + ft[theta]t + fR[theta]R with two constraints: 1 > or = fj > or = 0 and sigma fj = 1. The subscripts H, beta, t, and R refer to the helix, beta-form, beta-turn, and unordered form. The fractions, fj's, of 15 proteins are based on X-ray crystallography, ft refers to the net beta-turn after cancelling those residues having dihedral angles of opposite sign. The [theta]H infinity of an infinite helix and its chain-length dependence factor, k, were computed from the myoglobin data (Chen et al., 1974, Biochemistry 13, 3350). The average number of residues per helical segment, n, for 15 proteins was about 10, which can be used for proteins of unknown structure. The reference spectra of other three structural elements are computed by a least-squares method. Once the reference spectra are chosen, the same equation above can be used to estimate the fractions of the secondary structure of a protein from its CD data points between 190 and 240 nm at 1-nm intervals. The computed helical content is usually good to excellent (concanavalin A is a notable exception). Inclusion of the beta-turn in the analysis improves the correlation for the estimates of the beta-form, but the computed beta t values are not significantly correlated with the X-ray results. Matrix formulation proves the equivalence of the least-squares method and the integral curve-fitting.

Animals↗
PubMed1977

The shape of myosin subfragment-1. A equivalent oblate ellipsoid model based on hydrodynamic properties.

The molecular weights of the two heads of myosin subfragment-1, S-1(A1) and S-1(A2), based on sedimentation equilibrium are 120 000 and 110 000. Hydrodynamically, the two heads are indistinguishable, with intrinsic viscosity, [eta], of 0.064-0.065 dL/g and sedimentation coefficient, s(0)20,w, of 5.8 S. Together with the rotational correlation time taken from the literature (235 ns), all three hydrodynamic properties can be better fitted with an equivalent oblate ellipsoid of revolution than a prolate model. The width of the equatorial axis of the ellipsoid is about 135 A (the axial ratio is about 6). Probably, the S-1(A1) and S-1(A2) molecules have a half-doughnutlike or a flattened pearlike shape rather than an elongated one.

Animals↗