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K Uma

Publications and source records attributed to K Uma.

33 records · Page 2Linked to original sources
PubMed1989

Modular design of synthetic protein mimics. Characterization of the helical conformation of a 13-residue peptide in crystals.

The incorporation of alpha-aminoisobutyryl (Aib) residues into peptide sequences facilitates helical folding. Aib-containing sequences have been chosen for the design of rigid helical segments in a modular approach to the construction of a synthetic protein mimic. The helical conformation of the synthetic peptide Boc-Aib-(Val-Ala-Leu-Aib)3-OMe in crystals is established by X-ray diffraction. The 13-residue apolar peptide adopts a helical form in the crystal with seven alpha-type hydrogen bonds in the middle and 3(10)-type hydrogen bonds at either end. The helices stack in columns, zigzag rather than linear, by means of direct NH...OC head to tail hydrogen bonds. Leucyl side chains are extended on one side of the helix and valyl side chains on the other side. Water molecules form hydrogen bonds with several backbone carbonyl oxygens that also participate in alpha-helix hydrogen bonds. There is no apparent distortion of the helix caused by hydration. The space group is P2(1)2(1)2(1), with a = 9.964 (3) A, b = 20.117 (3) A, c = 39.311 (6) A, Z = 4, and dx = 1.127 g/cm3 for C64H106N13O16.1.33H2O. The final agreement factor R was 0.089 for 3667 data observed greater than 3 sigma(F) with a resolution of 0.9 A.

Crystallization↗
PubMed1989

Conformations of dehydrophenylalanine containing peptides: nmr studies of an acyclic hexapeptide with two delta Z-Phe residues.

The conformation of an acyclic dehydrophenylalanine (delta Z-Phe) containing hexapeptide, Boc-Phe-delta Z-Phe-Val-Phe-delta Z-Phe-Val-OMe, has been investigated in CDCl3 and (CD3)2SO by 270-MHz 1H-nmr. Studies of NH group solvent accessibility and observation of interresidue nuclear Overhauser effects (NOEs) suggest a significant solvent-dependent conformational variability. In CDCl3, a population of folded helical conformations is supported by the inaccessibility to solvent of the NH groups of residues 3-6 and the detection of several NiH----Ni + 1H NOEs. Evidence is also obtained for conformational heterogeneity from the detection of some Ci alpha H----Ni + 1H NOEs characteristic of extended strands. In (CD3)2SO, the peptide largely favors an extended conformation, characterized by five solvent-exposed NH groups and successive Ci alpha H----Ni + 1H NOEs for the L-residues and Ci beta H----Ni + 1H NOEs for the delta Z-Phe residues. The results suggest that delta Z-Phe residues do not provide compelling conformational constraints.

Magnetic Resonance Spectroscopy↗
PubMed1989

Solvated helical backbones: x-ray diffraction study of Boc-Ala-Leu-Aib-Ala-Leu-Aib-OMe.H2O.

A second example of insertion of a water molecule into the helical backbone of an apolar peptide is presented here and compared to a similar occurrence in a longer peptide with the same type of sequence of residues, i.e., Boc-Aib-(Ala-Leu-Aib)3-OMe. The backbone of the title compound assumes an approximate 3(10)-helical form with three 4----1 hydrogen bonds. In the place of a fourth 4----1 hydrogen bond, a water molecule is inserted between O(1) and N(4), and acts as a bridge by forming hydrogen bonds N(4) ... W(1) (2.95 A) and W(1) ... O(1) (2.81 A). The water molecule participates in a third hydrogen bond with a neighboring peptide molecule, W(1) ... O(4) (2.91 A). The insertion of the water molecule causes the apolar peptide to mimic an amphiphilic helix. Crystals grown from ethyl acetate/petroleum ether (reported here) or from methanol/water solution are in space group P2(1)2(1)2(1) with a = 12.024(4) A, b = 15.714(6) A, c = 21.411(7) A, Z = 4 and dcalc = 1.124 g/cm3 for C32H58N6O9.H2O. The overall agreement factor R is 6.3% for 2707 reflections observed with intensities greater than 3 sigma(F) and the resolution is 0.90 A.

Models, Molecular↗
PubMed1989

Conformations of peptides containing Z-alpha,beta-dehydroleucine (delta ZLeu). A comparison of Boc-Pro-delta ZLeu-Gly-NHEt and Boc-Pro-delta ZPhe-Gly-NHEt.

Two tripeptides of the type Boc-Pro-delta ZX-Gly-NHEt (where X = Leu, Phe) have been synthesized and their solution conformations investigated by 270 MHz 1H n.m.r. and i.r. spectroscopy. These conformational studies indicated that delta ZLeu, similar to delta ZPhe, has a strong tendency to stabilize folded Type II beta-turn conformations when present at i + 2 position.

Leucine↗
PubMed1989

Alpha-helix and mixed 3(10)/alpha-helix in cocrystallized conformers of Boc-Aib-Val-Aib-Aib-Val-Val-Val-Aib-Val-Aib-OMe.

Two molecules of Boc-Aib-Val-Aib-Aib-Val-Val-Val-Aib-Val-Aib-OMe (where Boc is t-butoxycarbonyl and Aib is alpha-aminoisobutyryl) cocrystallize in a triclinic cell with different helical conformations. One molecule is completely alpha-helical with seven 5----1 intramolecular hydrogen bonds. It forms three head-to-tail NH...O = C hydrogen bonds to other molecules of the same conformation. The second molecule has a mixed 3(10)/alpha-helix conformation with three 4----1 hydrogen bonds and four 5----1 hydrogen bonds; furthermore, there is a helix reversal at both termini. The second molecule forms only two head-to-tail hydrogen bonds with molecules of the same type, and the N(3)H group does not participate in any hydrogen bonding. The two different types of helices occur in alternate sheets in the crystal, where each sheet is composed of adjacent rods of helices formed by head-to-tail hydrogen bonding. Within each sheet, containing helices of only one type of conformation, the helices aggregate in a parallel mode. Between the sheets of different helices, the aggregation is antiparallel. The peptide, with formula C51H92N10O13, crystallizes in space group P1 with Z = 2 and cell parameters a = 10.047 +/- 0.002 A, b = 16.684 +/- 0.003 A, c = 19.198 +/- 0.004 A, alpha = 80.30 degrees +/- 0.01 degrees, beta = 85.74 degrees +/- 0.01 degrees, and gamma = 83.03 degrees +/- 0.01 degrees; overall agreement factor R = 6.7% for 6053 data ([F0] greater than 3 sigma) and 0.96-A resolution.

Aminoisobutyric Acids↗
PubMed1989

The integrated approach of yoga: a therapeutic tool for mentally retarded children: a one-year controlled study.

Ninety children with mental retardation of mild, moderate and severe degree were selected from four special schools in Bangalore, India. Forty-five children underwent yogic training for one academic year (5 h in every week) with an integrated set of yogic practices, including breathing exercises and pranayama, sithilikarana vyayama (loosening exercises), suryanamaskar, yogasanas and meditation. They were compared before and after yogic training with a control group of 45 mentally retarded children matched for chronological age, sex, IQ, socio-economic status and socio environmental background who were not exposed to yoga training but continued their usual school routine during that period. There was highly significant improvement in the IQ and social adaptation parameters in the yoga group as compared to the control group. This study shows the efficacy of yoga as an effective therapeutic tool in the management of mentally retarded children.

Adolescent↗
PubMed1988

Simultaneous observation of positive and negative nuclear Overhauser effects in oligopeptides due to segmental motion.

Nuclear Overhauser effect (NOE) studies of the symmetrical cystine peptides (Formula: see text) (n = 1-3) in dimethylsulfoxide, have resulted in the simultaneous observation of both positive and negative NOEs. Positive NOEs are observed on the Trp C2H and C4H protons of the indole ring upon irradiation of Trp C alpha H and C beta H2 resonances in the peptides where n = 1 and 2. Negative NOEs are observed between backbone NH and C alpha H protons. The magnitudes of the observed NOEs are sensitive to changes in molecular size and solvent viscosity. The results demonstrate that NOEs may be a useful probe of sidechain segmental motion in oligopeptides.

Chemical Phenomena↗
PubMed1988

Aqueous channels within apolar peptide aggregates: solvated helix of the alpha-aminoisobutyric acid (Aib)-containing peptide Boc-(Aib-Ala-Leu)3-Aib-OMe.2H2O.CH3OH in crystals.

Although the peptide Boc-Aib1-Ala2-Leu3-Aib4-Ala5-Leu6-Aib7-Ala8-L eu9-Aib10-OME [with a t-butoxycarbonyl (Boc) blocking group at the amino terminus, a methyl ester (OMe) at the carboxyl terminus, and four alpha-amino-isobutyric (Aib) residues] has a 3-fold repeat of residues, the helix formed by the peptide backbone is irregular. The carboxyl-terminal half assumes an alpha-helical form with torsion angles phi and psi of approximately -60 degrees and -45 degrees, respectively, whereas the amino-terminal half is distorted by an insertion of a water molecule between the amide nitrogen of Ala5 [N(5)] and the carbonyl oxygen of Ala2 [O(2)]. The water molecule W(1) acts as a bridge by forming hydrogen bonds N(5)...W(1) (2.93 A) and W(1)...O(2) (2.86 A). The distortion of the helix exposes the carbonyl oxygens of Aib1 and Aib4 to the outside environment, with the consequence that the helix assumes an amphiphilic character despite having all apolar residues. Neighboring helices in the crystal run in antiparallel directions. On one side of a helix there are only hydrophobic contacts with efficient interdigitation of leucine side chains with those from the neighboring helix. On the other side of the helix there are hydrogen bonds between protruding carbonyl oxygens and four water molecules that separate two neighboring helices. Along the helix axis the helices bind head-to-tail with a direct hydrogen bond N(2)...O(9) (3.00 A). Crystals grown from methanol/water solution are in space group P21 with a = 15.778 +/- 0.004 A, b = 11.228 +/- 0.002 A, c = 18.415 +/- 0.003 A, beta = 102.10 +/- 0.02 degrees, and two formula units per cell for C49H88N10O13.2H2O.CH3OH. The overall agreement factor R is 7.5% for 3394 reflections observed with intensities greater than 3 sigma (F), and the resolution is 0.90 A.

Aminoisobutyric Acids↗
PubMed1988

Conformations of dehydrophenylalanine containing peptides. Nuclear Overhauser effect study of two acyclic tetrapeptides.

Two isomeric, acyclic tetrapeptides containing a Z-dehydrophenylalanine residue (delta Z-Phe) at position 2 or 3, Boc-Leu-Ala-delta Z-Phe-Leu-OMe (1) and Boc-Leu-delta Z-Phe-Ala-Leu-OMe (2), have been synthesized and their solution conformations investigated by 270 MHz 1H n.m.r. spectroscopy. In peptide 1 the Leu(4) NH group appears to be partially shielded from solvent, while in peptide 2 both Ala(3) and Leu(4) NH groups show limited solvent accessibility. Extensive difference nuclear Overhauser effect (n.O.e.) studies establish the occurrence of several diagnostic inter-residue n.O.e.s (Ci alpha H----Ni+1H and NiH----Ni+1H) between backbone protons. The simultaneous observation of "mutually exclusive" n.O.e.s suggests the presence of multiple solution conformations for both peptides. In peptide 1 the n.O.e. data are consistent with a dynamic equilibrium between an -Ala-delta Z-Phe- Type II beta-turn structure and a second species with delta Z-Phe adopting a partially extended conformation with psi values of +/- 100 degrees to +/- 150 degrees. In peptide 2 the results are compatible with an equilibrium between a highly folded consecutive beta-turn structure for the -Leu-delta Z-Phe-Ala- segment and an almost completely extended conformation.

Indicators and Reagents↗
PubMed1988

Aggregation studies in crystals of apolar helical peptides: Boc-Aib-Val-Ala-Leu-Aib-Val-Ala-Leu-Aib-OMe.

In the crystal, the backbone of Boc-(Aib-Val-Ala-Leu)2-Aib-OMe adopts a helical form with four alpha-type hydrogen bonds in the middle, flanked by 3(10)-type hydrogen bonds at either end. The helical molecules stack in columns with head-to-tail hydrogen bonds, either directly between NH and CO, or bridged by solvent molecules. The packing of the helices is parallel, even in space group P2(1). Cell parameters are a = 9.837(2) A, b = 15.565(3) A, c = 20.087(5) A, beta = 96.42(2) degrees, dcalc = 1.091 g/cm3 for C46H83N9O12.1.5H2O.0.67CH3OH. There appears to be some hydration of the backbone in this apolar helix.

Chemical Phenomena↗
PubMedDate not supplied

Peptide design: influence of a guest Aib-Pro segment on the stereochemistry of an oligo-val sequence--solution conformations and crystal structure of Boc-(Val)2-Aib-Pro-(Val)3-OMe.

The peptide Boc-Val-Val-Aib-Pro-Val-Val-Val-OMe has been synthesized to investigate the effect of introduction of a strong beta-turn promoting guest segment into an oligopeptide with a tendency to form extended structures. 1H-nmr studies in solution using analysis of NH group solvent accessibility and nuclear Overhauser effects suggest an appreciable solvent dependence of conformations. In chloroform a 3(10)-helical structure is favored, while in dimethylsulfoxide an Aib-Pro beta-turn with extended arms on either side is suggested. In the crystal, the backbone forms a somewhat distorted 3(10)-helix despite the presence of a Pro residue in the middle. Among the four possible intrahelical hydrogen bonds three are of the 4----1 type and one 5----1. Head-to-tail NH...O = C hydrogen bonds link the helical molecules into continuous columns. The space group is P2(1)2(1)2(1) a = 11.320(2), b = 19.889(3), and c = 21.247(3) A.

Amino Acid Sequence↗
PubMedDate not supplied

Effects of end group and aggregation on helix conformation: crystal structure of Ac-(Aib-Val-Ala-Leu)2-Aib-OMe.

The role of end groups in determining stereochemistry and packing in hydrophobic helical peptides has been investigated using an alpha-aminosobutyric acid (Aib) containing model nonapeptide sequence. In contrast to the Boc-analogue, Ac-(Aib-Val-Ala-Leu)2-Aib-OMe crystallizes with two independent molecules in a triclinic cell. The cell parameters are: space group P1, a = 10.100(2)A, b = 15.194(4)A, c = 19.948(5)A, alpha = 63.12(2) degrees, beta = 88.03(2) degrees, y = 88.16(2) degrees, Z = 2, R = 7.96% for 5140 data where magnitude of Fo > 3 rho(F). The two independent molecules alternate in infinite columns formed by head-to-tail hydrogen bonding. The helices in the two independent molecules are quite similar to each other but one molecule is rotated approximately 123 degrees about its helix axis with respect to the other. All the helical columns pack parallel to each other in the crystal. Replacement of the bulky Boc group does not lead to any major changes in conformation. Packing characteristics are also similar to those observed for similar helical peptides.

Crystallization↗
PubMedDate not supplied

Isolated involvement of the mandible by non-Hodgkin's lymphoma.

A case report of isolated involvement of the mandible by non-Hodgkin lymphoma is presented. The patient presented with a non-healing ulcer following a tooth extraction. Biopsy revealed an undifferentiated cancer. Investigations failed to reveal any involvement of the organs. A hemimandibulectomy was performed followed by radiotherapy on receipt of the histopathological diagnosis of non-Hodgkin lymphoma. The patient is asymptomatic two and a half years after treatment.

Biopsy, Needle↗
PubMedDate not supplied

Visceral larva migrans.

We present a case of visceral larva migrans which came as a complete histologic surprise. The patient was operated as a case of chronic cholecystitis and was found at operation to have multiple hepatic nodules. A cholecystectomy with a biopsy of the liver nodule was performed. Histopathologically a diagnosis of visceral larva migrans was made. To our knowledge this is the first case report of the disorder from India. A discussion based on the review of literature is presented.

Biopsy↗