Search PubMed⌕ Search

Biomedical subjects

M Goodman

Publications and source records attributed to M Goodman.

At least 541 records · Page 30Linked to original sources
PubMed1966

Polymorphism of lactate dehydrogenase in gelada baboons.

In a group of 21 gelada baboons, three different lactate dehydrogenase patterns were observed after starch-gel electrophoresis of tissue extracts. The patterns indicate that a mutation has occurred in this population in the gene responsible for the A-subunit. The normal and variant homozygotes each contain five isozymes, those containing the A subunit having characteristically different electrophoretic mobilities. The heterozygote contains the expected 15 isozymes.

Animals↗
PubMedDate not supplied

Conformational analysis of the dipeptide taste ligand L-aspartyl-D-2-aminobutyric acid-(S)-alpha-ethylbenzylamide and its analogues by NMR spectroscopy, computer simulations and X-ray diffraction studies.

A dipeptide taste ligand L-aspartyl-D-2-aminobutyric acid-(S)-alpha-ethylbenzylamide was found to be about 2000 times more potent than sucrose. To investigate the molecular basis of its potent sweet taste, we carried out conformational analysis of this molecular and several related analogues by NMR spectroscopy, computer simulations and X-ray crystallographic studies. The results of the studies support our earlier model that an L-shape molecular array is essential for eliciting sweet taste. In addition, we have identified an aromatic group located between the stem and the base of the L-shape, which is responsible for enhancement of sweetness potency. In this study, we also assessed the optimal size of the essential hydrophobic group (X) and the effects of the chirality of the second residue toward taste.

Aminobutyrates↗
PubMedDate not supplied

A conformational comparison of two stereoisomeric cyclic dermorphin analogues employing NMR and computer simulations.

In a continuation of our program to study the structure-activity relationship of peptide opiates, we report the conformational analysis of two cyclic tetrapeptides related to dermorphin--Tyr-c[D-Orn-Phe-Asp]-NH2 and Tyr-c[D-Asp-Phe-Orn]-NH2. These analogues have similar binding properties marked by a high selectivity for the mu-opioid receptors because of a drastic decrease in the affinity for the delta-opioid receptor. The conformational preferences of these analogues of dermorphin determined from proton nmr, molecular dynamics, and energy minimizations are quite similar. The constraint of the 13-membered ring formed from cyclization is quite evident from the conformational analysis. The constrained ring system acts as a template maintaining the relative orientation of the exocyclic tyrosine and side chain of phenylalanine. Two intramolecular hydrogen bonds measured for the D-Orn analogue in DMSO were disrupted upon the addition of water. For the D-Asp analogue, two intramolecular hydrogen bonds were found stable in DMSO and water. The global conformations of the two peptides determined from nuclear Overhauser effects did not change with the solvent titration. The difference in the hydrogen bonding within the 13-membered ring may account for the slight differences observed in the efficacy of the analogues at the mu-opioid receptors.

Amino Acid Sequence↗
PubMedDate not supplied

Depsipeptide analogues of elastin repeating sequences: synthesis.

Depsipeptide analogues of peptide sequences can help in elucidating the role of specific hydrogen bonds in determining the conformation in peptides. The repeating pentapeptide and hexapeptide sequences of elastin have been suggested to contain a type II beta-turn with a 4----1 hydrogen bond. Depsipeptide analogues of the repeating sequences of elastin in which this 4----1 hydrogen bond cannot exist were synthesized. A fragment condensation approach was employed in which the depsipeptide ester bond was introduced early in the synthesis. This approach proved to be effective, although the increased lability of the depsipeptide ester bond resulted in side products and low yields in some reactions.

Amino Acid Sequence↗
PubMedDate not supplied

Depsipeptide analogues of elastin repeating sequences: conformational analysis.

In this work the effect of elimination of a specific hydrogen bond on the conformation of the repeating peptides of elastin was studied. These repeating sequences are the pentapeptide Val-Pro-Gly-Val-Gly and the hexapeptide Val-Ala-Pro-Gly-Val-Gly. These sequences have been proposed to occur in a beta-turn conformation with a hydrogen bond involving the amide NH of the internal valine residue and the carbonyl oxygen of the residue preceding proline. In the depsipeptide analogues studied in this work, this 4-1 beta-turn hydrogen bond cannot occur. We studied the depsipeptide sequences Val-Pro-Gly-Hiv-Gly and Val-Ala-Pro-Gly-Hiv-Gly (Hiv denotes S-alpha-hydroxyisovaleric acid, the hydroxy acid analogue of valine), as well as the peptide sequences Val-Pro-Gly-Val-Gly and Val-Ala-Pro-Gly-Val-Gly. Compounds studied included sequences with the Boc and benzyl ester protecting groups, derivatives with the acetyl and N-methylamide end groups and polymers of the above sequences. Our conclusions are based on a comparison of depsipeptides with analogous peptides. Conformational analysis was carried out by nmr, CD, and ir spectroscopy. We propose that in the repeating sequences of elastin an equilibrium exists between a gamma-turn structure and a beta-turn structure in the Pro-Gly segment resulting in a structure that combines flexibility with strong conformational preferences. The C7 involves the amide NH of the internal glycine and the carbonyl oxygen of the residue preceding proline. In the N-methylamide derivatives a similar equilibrium exists in the Gly-Val-Gly segment. In the depsipeptides the beta-turn cannot occur and only the gamma-turn is seen. In the polydepsipeptides the major conformational feature is a type I beta-turn involving Gly5 NH and Pro CO.

Amino Acid Sequence↗
PubMedDate not supplied

Highly potent side chain-main chain cyclized dermorphin-deltorphin analogues: an integrated approach including synthesis, bioassays, NMR spectroscopy and molecular modelling.

Our continuing efforts to study structure-activity relationships of peptide opioids have resulted in the synthesis of a series of cyclic opioids related to dermorphins and deltorphins. The biological activities of the compounds have been determined and the conformational analyses carried out using 1H-NMR spectroscopy and molecular modelling. The three compounds in the series Tyr-c[D-Orn-Phe-Ala], Tyr-c[D-Lys-Phe-Ala], and Tyr-c[A2bu-Phe-Ala-Leu] are cyclized via a lactam bridge from the side-chain of the residue at the second position with the carboxyl terminus of each compound. The molecules incorporate 12-, 13- and 14-membered rings, respectively. They include a phenylalanine at the third position which is a distinguishing characteristic of dermorphins and deltorphins. The guinea pig ileum and mouse vas deferens assays show that the compounds are highly active at both mu- and delta-opioid receptors. The compounds are all highly effective antinociceptive agents as measured by the intrathecal rat hot plate test. Conformational analyses of the molecules indicate that they can adopt topochemical arrays required for bioactivity at both mu- and delta-receptors which explains their high activity in both guinea pig ileum and mouse vas deferens in vitro assays. The results support our models for mu- and delta-receptor activity for constrained peptide opioids.

Amino Acid Sequence↗
PubMedDate not supplied

Sweet and bitter taste: structure and conformations of two aspartame dipeptide analogues.

The synthesis and X-ray diffraction analysis of two dipeptide taste ligands have been carried out as part of our study of the molecular basis of taste. The compounds L-aspartyl-D-alpha-methylphenylalanine methyl ester [L-Asp-D-(alpha Me)Phe-OMe] and L-aspartyl-D-alanyl-2,2,5, 5-tetramethylcyclopentanyl ester [L-Asp-D-Ala-OTMCP] elicit bitter and sweet taste, respectively. The C-terminal residues of the two analogues adopt distinctly different conformations in the solid state. The aspartyl moiety assumes the same conformation found in other dipeptide taste ligands with the side-chain carboxylate and the amino groups forming a zwitterionic ring with a conformation defined by psi, chi 1 = 157.7 degrees, -61.5 degrees for L-Asp-D-Ala-OTMCP and 151.0 degrees, -68.8 degrees for L-Asp-D-(alpha Me)Phe-OMe. In the second residue, a left-handed helical conformation is observed for the (alpha Me)Phe residue of L-Asp-D-(alpha Me)Phe-OMe with phi 2 = 49.0 degrees and psi 2 = 47.9 degrees, while the Ala residue of L-Asp-D-Ala-OTMCP adopts a semi-extended conformation characterized by dihedral angles phi 2 = 62.8 degrees and psi 2 = -139.9 degrees. The solid-state structure of the bitter L-Asp-D-(alpha Me)Phe-OMe is extended: while the crystal structure of the sweet L-Asp-D-OTMCP roughly adopts the typical L-shaped structure shown by other sweeteners. The data of L-Asp-D-(alpha Me)Phe-OMe are compared with those of its diastereoisomer L-Asp-L-(alpha Me)Phe-OMe. Conformational analysis of the two taste ligands in solution by NMR and computer simulations agrees well with our model for sweet and bitter tastes.

Aspartame↗
PubMedDate not supplied

Could implantable cardioverter defibrillators provide a human model supporting the learned helplessness theory of depression?

Affective symptoms were examined retrospectively in 25 patients following placement of implantable cardioverter defibrillators (ICD) which can produce intermittent shocks without warning in response to cardiac ventricular arrhythmias. The number of ICD random, uncontrollable discharge shocks and pre-ICD history of psychological distress (i.e., depression and/or anxiety) were documented in all patients using a demographics questionnaire and a standardized behavioral/psychological symptoms questionnaire (i.e., Symptom Checklist-90 Revised). ICD patients were dichotomized into two groups: those without a history of psychological distress prior to ICD (n = 18) and those with a history of psychological distress prior to ICD (n = 7). In ICD patients without a prior history, results indicated that quantity of ICD discharge shocks was significantly predictive of current reported depression (r = 0.45, p = 0.03) and current reported anxiety (r = 0.51, p = 0.02). Conversely, in patients with a reported history of psychological distress, there was no significant relationship found between quantity of discharge shocks and current reported depression or anxiety. This study may provide evidence in support of a human model of learned helplessness in that it supports the notion that exposure to an unavoidable and inescapable aversive stimulus was found to be related to patients' reported depression. Further studies may wish to prospectively consider a larger sample as well as a more comprehensive assessment of premorbid psychological symptoms.

Adult↗
PubMedDate not supplied

Temporal relationship modeling: DTP or DT immunizations and infantile spasms.

The time relationship between DTP immunization and infantile spasms (IS) onset was examined using three models--association, temporal shift, and no-effect--and the case/control data from the National Childhood Encephalopathy Study (NCES). Infantile spasms cases classified as being previously abnormal (e.g., tuberous sclerosis complex patients) showed a no-effect relationship, whereas those classified as previously normal suggested a fit to the temporal shift model, i.e. no increase in number of cases but a shortening of time to onset of seizure. No data fit the association model. Analyses for vaccine complications should examine for temporal changes (i.e. temporal shift) in addition to increased risks.

Child, Preschool↗
PubMedDate not supplied

Solid phase organic synthesis of piperazinone containing enkephalin mimetics: a readily derivatized, traceless scaffold.

The solid phase synthesis of a series of piperazinone-derived Leu-enkephalin analogues is presented. The initial step in the synthesis involved the N-alkylation of Wang resin bound N-(4-tert-butyloxy-phenethyl)-glycine with D or L Boc-serine-beta-lactone (the Vederas lactone). The resulting carboxylic acid was then coupled to a variety of monosubstituted benzylamine derivatives using benzotriazol-1-yloxy-tris(dimethyl-amino)phosphonium hexafluorophosphate (the BOP reagent) to yield a series of resin bound tertiary amides. Treatment with 5% H2O in TFA resulted in the facile cleavage, deprotection, and cyclization of this linear precursor to yield a series of piperazinones (compounds 1-8).

Drug Design↗