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Biomedical subjects

I D Rae

Publications and source records attributed to I D Rae.

9 recordsLinked to original sources
PubMed1992

Chemical design of peripherally acting compounds.

1. Some guanidines, related in structure to mianserin and to 2-methyl-1,2,9,13b-tetrahydro-3H-dibenz[c,f]imadazo[1,5a] azepin-3-imine hydrobromide (WAL 801), have been synthesized and shown to be peripherally acting 5-HT2 antagonists. Structurally related compounds but not bearing a charged ionic group have been shown to have central activity. 2. Computer-aided molecular modelling has been used to establish a 5-HT2 pharmacophore. 3. The principle of exclusion from the CNS by incorporating a highly polar group to a biologically active molecule has been extended to the design and synthesis of a peripherally acting analgesic.

Computer Simulation↗
PubMed1990

Identification of the aspartimide structure in a previously-reported peptide.

The octapeptide Leu-Ser-Arg-Leu-Phe-Asp-Asn-Ala (hGH 6-13) has been reported to show insulin-potentiating properties, and its synthesis by conventional solid-phase synthesis was previously described. It is now shown that peptide synthesized with diisopropylethylamine or N-methylmorpholine as neutralizing base in each cycle does have the above structure. When triethylamine was used as neutralizing base however, the Asp residue was converted to its imide, the presence of which has been demonstrated by means of infrared, 1H-NMR and fast-atom bombardment mass spectra, and by reactivity studies, electrophoresis at several pH values, and enzymic hydrolysis. Only the imide form of the peptide possesses the previously reported biological properties. A study of imide formation from protected and unprotected peptides showed that cyclization occurred during a wide range of acid and base treatments, but 10% triethylamine in CH2Cl2 was most effective, producing over 40% of imide in 90 min. The results of the investigation are compared with others in the literature, including those for the peptide hormone secretin.

Amino Acid Sequence↗
PubMed1987

Isolation of opiate receptor ligands in coffee.

1. We have reported previously that instant coffee contains ligands for opiate receptors with characteristics similar to those of opiate antagonists. 2. A concentrate of receptor-active ligands from instant coffee was prepared by serial treatments involving Amberlite XAD-2, flash chromatography and gel permeation chromatography. 3. Examination of the final concentrate by GC-MS showed the presence of a number of isomeric (iso)feruloylquinic acid lactones. 4. It is suggested that the synthesis and biological testing of each quinide isomer will establish which is responsible for the opiate receptor activity of instant coffee.

Animals↗
PubMed1979

Cyclized dipeptide model for a beta-bend.

A cyclic dipeptide in which L-Ala-Gly was cyclized with epsilon-aminocaproic acid has been synthesized as a model for a beta-bend. Its conformational properties have been examined by means of conformational energy calculations and nuclear magnetic resonance, infrared, Raman, and circular dichroism spectroscopy in various solvents. These calculations and experiments suggest that a type II beta-bend exists in the Ala-Glymoiety, with an NH...O = C hydrogen bond in the epsilon-aminocaproic acid portion of the molecule, and that the molecule adopts a unique conformation in solution. In contrast, an open-chain analog of this compound exists in solution as an ensemble of conformations but with a significant amount of a type II beta-bend structure in the ensemble.

Circular Dichroism↗
PubMed1979

H and 13C nuclear magnetic resonance spectra of some peptides with fibrinogen-like reactivity.

The 1H and 13C spectra of four peptides, L-Phe-Val-Arg-pNA, D-Phe-Val-Arg-pNA, L-Phe-Pip-Arg-pNA and D-Phe-Pip-Arg-pNA (pNA = p-nitroaniline, Pip = pipecolic acid residue), have been examined, and deductions made about their conformation in solution. The D-Phe peptides, which are cleaved especially rapidly by thrombin in water, have structures (in deuterated DMSO) in which the aromatic ring of the D-Phe residue is folded back over the Val or Pip residue. This arrangement is not found in the L-Phe peptides. It is proposed that this feature (in which Phe could be situated near Val and near the Arg-Gly bond of the A alpha chain in the three-dimensional structure of fibrinogen) may be especially advantageous for binding to the enzyme.

Amino Acid Sequence↗
PubMed1978

Nuclear magnetic resonance study of fibrinogen-like peptides and their structure in dimethyl sulfoxide and water.

The 1H nuclear magnetic resonance (NMR) spectra of four fibrinogen-like oligopeptides (H-Gly-Pro-Ala-NH2, H-Arg-Gly-Pro-Ala-NH2, H-Val-Arg-Gly-Pro-Ala-NH2, and H-Gly-Val-Arg-Gly-Pro-Ala-NH2) in dimethyl-d6 sulfoxide (Me2SO-d6), and of the hexapeptide in water, and the 13C NMR spectrum of H-Gly-Pro-Ala-NH2 in Me2SO-d6, were recorded and interpreted in terms of preferred conformations in solution. Each peptide exists in Me2SO-d6 as in a 30:70 mixture of cis and trans isomers about the Gly-Pro bond, and the hexapeptide in water is solely the trans isomer. For the trans isomers in Me2SO-d6, there is a hydrogen bond between the Gly CO group and one of the C-terminal primary amide hydrogens, and a beta turn involving the Gly-Pro-Ala-NH, section of the molecules. A strong NOE between Pro CalphaH and Ala NH for the trans isomer of the tripeptide in Me2SO-d6 completes the identification of this structural feature as a type II beta turn.

Dimethyl Sulfoxide↗
PubMedDate not supplied

Synthesis and evaluation of constrained peptide analogues related to the N-terminal region of human growth hormone.

The synthesis and incorporation of two different isomeric gamma-lactam structures into peptide analogues related to hGH [6-13] are described. These peptide analogues and the corresponding aspartimide analogue have been tested for hypoglycemic activity with the intravenous insulin tolerance test. One lactam structure is of the type developed by Freidinger and co-workers, while the isomeric gamma-lactam structure represents a new constrained synthon for use in peptide synthesis. We have found that the hGH [6-13] peptide analogue incorporating the Freidinger lactam was more potent and longer lasting than the aspartimide peptide analogue. The hGH [6-13] peptide analogue incorporating the new gamma-lactam has diminished hypoglycemic activity. The relative biological activities of the three peptide analogues and the possible conformational implications at the physiological site of action are discussed.

Amino Acid Sequence↗