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Biomedical subjects

C R Beddell

Publications and source records attributed to C R Beddell.

46 records · Page 3Linked to original sources
PubMed1977

Symmetrical features in polypeptide hormone-receptor interactions.

Symmetrical features were observed in the amino acid sequences of some biologically active peptides. It is suggested that this approximate symmetry is reflected in the conformations of the peptides at their respective biological receptors, and has arisen by natural selection as both peptides and receptors evolved to optimise their mutual fit. It follows that the binding site for each peptide at its receptor would share the same symmetry element. This would arise if the peptide binds to two symmetrically related similar or identical submits in the receptor.

Amino Acid Sequence↗
PubMed1977

A conformational analysis for leucine-enkephalin using activity and binding data of synthetic analogues.

1. Leucine-enkephalin and some analogues were assayed for activity in vitro on the mouse vas deferens and for binding to opiate receptors from rat brain. 2. The experimental data were analysed in terms of the stringency for glycine, a D-amino acid or an L-amino acid at each position in the peptide. 3. The observed configurational specificity was compared with the stringency that would be predicted to occur if enkephalin adopted certain hydrogen-bonded conformations at the receptor. 4. A small subset of the conformations examined was found to be compatible with the experimental data.

Animals↗
PubMed1976

Compounds designed to fit a site of known structure in human haemoglobin.

1 The three-dimensional coordinates of the atoms in human haemoglobin are known, and there is a specific site in the deoxygenated form of the protein at which 2,3-diphosphoglycerate (DPG) interacts. 2 Molecular models of this site have been constructed and used to design compounds which should bind to the deoxy conformation and stabilize it. These compounds should therby promote oxygen liberation, as does DPG. 3The compounds so designed were found to promote oxygen liberation. Their relative potencies, as assessed by sigmoidal dose-response curves, are in the predicted sequence.

Benzyl Compounds↗
PubMed1975

Pseudosymmetry in the structure of luteinizing hormone-releasing hormone. Studies on a series of novel analogs.

Pseudosymmetry in the LH-RH structure is described. Eleven analogs of LH-RH (SMALLER THAN Glu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2) have been synthesized by the fragment condensation method and the repetitive excess mixed anhydride method. Multiple substitutions have been made in the LH-RH sequence, which retain the pseudosymmetry of the LH-RH molecule, while presenting fewer problems of synthesis than the corresponding residues in the natural decapeptide. Thus Trp3, Ser4, Tyr5, Gly6, Leu7, and Arg8 residues were replaced by amino acids having similar properties to the residues that they replace. In all but one of the peptides the Gly10-NH2 residue was replaced by ethylamide, while in the remaining peptide, 1-methyl-5-aminomethyltetrazole (AMT-Me) was substituted at position 10. The compounds were assayed in vitro and in vivo. The following analogs had in vivo and in vitro activities in the range 1-28 percent relative to LH-RH: I, smaller than Glu-His-Phe-Ala-Tyr-Gly-Leu-Arg-Pro-NHEt; II, smaller than Glu-His-Phe-Gly-Tyr-Gly-Leu-Arg-Pro-NHEt; VII, smaller than Glu-His-Phe-Ala-Tyr-Gly-Phe-Arg-Pro-NHEt; IX, smaller than Glu-His-Phe-Ala-Tyr-D-Ala-Leu-Arg-Pro-NHEt; XI, smaller than Glu-His-Phe-Gly-Tyr-Gly-Leu-Arg-Pro-AMT-Me.

Amino Acid Sequence↗
PubMedDate not supplied

NMR spectroscopy of human post mortem cerebrospinal fluid: distinction of Alzheimer's disease from control using pattern recognition and statistics.

1H NMR spectra have been measured at 500 and 600 MHz on 23 human cerebrospinal fluid samples obtained at autopsy from Alzheimer's disease patients and controls. The spectra at 500 MHz were quantified using 42 descriptors based on NMR peak heights and it was shown that differences between the two classes were apparent in the delta 2.4-2.9 region. Remeasured at 600 MHz a detailed examination of this chemical shift range identified citrate, aspartate, N-acetyl aspartate, methionine and glutamate in this region of the spectra. Principal components analysis showed that a separation of the two classes was possible and detailed statistics indicated that citrate level was the principal marker. Patient age and the interval between death and autopsy (parameters not closely matched between the two groups) were examined statistically to establish whether these might account for the citrate differences. Although they could possibly account for them to some extent, the relationship between citrate levels and disease state remained significant at p < 0.05. The data invite a test of the importance of citrate levels in Alzheimer's disease using samples taken ex vivo.

Aged↗