Conformation and structure of linear peptides with regularly alternating l- and d-residues: structure of the blocked hexapeptide tert-butyloxycarbonyl-(d-alloisoleucyl-l-isoleucyl)3 methyl ester monohydrate

Peptides with a regular sequence of enantiomeric residues (l and d ) along the chain have received considerable attention because of their accessibility to unique conformations and because they are model compounds for the naturally occurring peptide gramicidin A, which shows monovalent cation selective transmembrane transport. The solid-state structure of the linear hexapeptide t-Boc-(d -aIle-l -Ile)₃-OMe has been determined by X-ray diffraction techniques and refined to a final R factor of 0.068. The molecule shows a bent U-shaped conformation stabilized by three intramolecular H-bonds of the N—H?O=C type: a type II β-bend (4 → 1 bend or C₁₀ ring structure) with l -Ile² and d -aIle³ at positions 2 and 3 of the bend, an α-turn (5 → 1 bend or C₁₃ ring structure) and a 1 → 5 bend or C₁₇ ring structure. The first two 10-membered and 13-membered bends are enclosed in the latter 17-membered hydrogen-bonded ring structure. This structural motif is common to hepta- and octa-peptide cyclic molecules, showing that ring closure is not required to achieve a particular topology in the molecular design of specific bended conformations. © Munksgaard 1995.     

CONFORMATIONAL ANALYSIS OF N-(tert.-AMYLOXYCARBONY-l-PROLINE IN THE SOLID STATE AND IN SOLUTION

The solid-state conformational analysis of t-AOC-l -Pro-OH** has indicated that the molecules are not folded up to form an oxy-C₇ peptide conformation, but rather that they are held together through intermolecular O-H. 0 = C (urethane) hydrogen bonds. The tertiary amide bond is in the cis configuration. In solvents of high polarity strongly solvated species largely predominate. In cyclohexane solution non-associated and associated (involving the carboxyl C = O as the proton acceptor) species are simultaneously present. Obviously, the extent of association increases with increasing solute concentration. The amount of the oxy-C₇ form, if any, should be extremely small. It is also demonstrated that CD measurements alone can lead to an incorrect picture of the conformational preferences of amino acid derivatives and small peptides in solution.     

Solid-phase synthesis of sauvagine-(17–40)

The solid-phase synthesis of the tetracosapeptide corresponding to the C -terminal amino acid sequence of sauvagine is described. After purification by gel filtration, the polypeptide appeared to possess an acceptable degree of homogeneity, as judged by different kinds of electrophoresis and chromatography, and by automated Edman degradation analysis. Preliminary pharmacological results indicate that the fragment-(17–40) is practically devoid of any sauvagine activity on the circulatory system and endocrine glands; a weak effect on gastric emptying delay has been demonstrated (1% of the natural product).     

Effect of lamotrigine on EEG paroxysmal abnormalities and background activity: a computerized analysis

1 Little information is available about the action of lamotrigine (LTG) on EEG paroxysmal abnormalities and background activity. On the contrary, several clinical trials have shown the therapeutic efficacy of the drug in preventing partial and generalized seizures.
2 We performed computerized EEG monitoring in 21 patients suffering from focal and generalized epilepsy before and 4 months after addition of LTG. The anticonvulsant modified the EEG ictal events by reducing their frequency and duration. A statistically significant decrease of the interictal spikes was observed. The decrease involved mainly the spreading component of the interictal events leading to a better spatial definition of the epileptic focus.
3 In the presence of LTG, generalized tonic-clonic attacks were completely controlled, whereas partial seizures were decreased.
4 The EEG background activity was not modified by the addition of the drug.
5 Our findings suggest a specific role for LTG in the generation and propagation processes of epileptiform activity without interfering with the EEG background activity.