Conformational investigation of αβ-dehydropeptides

Solution conformations of three series of model peptides, homochiral Ac-Pro-L-Xaa-NHCH₃ and heterochiral Ac-Pro-D-Xaa-NHcH₃ (Xaa = Val, Phe, Leu, Abu. Ah) as well as αβ-unsaturated Ac-Pro-ΔXaa-NHCH₃ [Δ Xaa =ΔVal, (Z)-ΔPhe, (Z)-ΔLeu, (Z)-ΔAbu] were investigated in CDCl₃ and CH₂Cl₂ by ¹H-, ¹³C-NMR, and FTIR spectroscopy. NH stretching absorption spectra, solvent shifts Δδ for NH (Xaa) and NHCH₃ on going from CDCl₃ to (CD₃)₂SO, diagnostic interresidue proton NOEs, and trans-cis isomer ratios were examined. These studies performed showed the essential difference in conformational propensities between homochiral peptides (L-Xaa) on the one hand and heterochiral (D-Xaa) and αβ-dehydropeptides (ΔXaa) on the other. Former compounds are conformationally flexible with an inverse γ-bend, a β-turn, and open forms in an equilibrium depending on the nature of the Xaa side chain. Conformational preferences of heterochiral and αβ-dehydropeptides are very similar, with the type-II β-turn as the dominating structure. There is no apparent correlation between conformational properties and the nature of the Xaa side chain within the two groups. The β-turn formation propensity seems to be somewhat greater in αβ-unsaturated than in heterochiral peptides, but an estimation of β-folded conformers is risky.     

Competition between tuftsin and HBV S-protein sequences

The syntheses of HBV S-protein partial sequences: Thr-Lys-Pro-Thr (I), Thr-Lys-Pro-Thr-Asp (II), and Thr-Lys-Pro-Thr-Asp-Gly (III) and also of pentapeptide Thr-Lys-Pro-Gly-Arg (IV), are described. For the peptides II and III inhibitory activity against tuftsin was found. Peptide IV (an analogue of tuftsin-inhibitor Thr-Lys-Pro-Pro-Arg) demonstrated a tuftsin-like activity in the phagocytosis experiments.     

The concept of superactive esters

According to the concept presented, esters forming an amide (peptide) bond by the mechanism S^#_nD_N or S^# * * The market price of synthetic peptides contains a very small component from the cost of the amino acids: obviously the main share consists of expenses related to their processing, which in the net result simply comprises dehydration leading to the formation of peptide bonds between amino acid residues. For oxytocin (Bachem H-6885) amino acids comprise less than 0.004% of the cost of the peptide.
_ND_N involving fast decay of the tetrahedral intermediate may behave as ‘superactive acylating reagents’. These should render coupling involving less reactive substrates, i.e. sterically hindered or ‘difficult coupling sequences’, much faster and more uniform than classic active esters. In extremely cases this advantage could be significant, and the calculated increase in time required for 99.9% coupling substrates 6 pK_a units less reactive than the standard ones reaches 2512000 τ_1/2 units for classic active esters, but only 631 τ_1/2 units for reaction involving ‘superactive esters’. The postulated change of mechanism is expected for esters bearing a leaving group which is able to undergo an additional, synchronous, energetically favored process accompanying its departure, as has been observed in the case of triazine esters. Some advantages of triazine superactive esters in the condensation of sterically hindered substrates are demonstrated.     

Left Atrial Size and Wall Motion in Patients with Permanent Ventricular and Atrial Pacing

KUBICA, J., ET AL.: Left Atrial Size and Wall Motion in Patients with Permanent Ventricular and Atrial Pacing. It is well known that during permanent ventricular pacing atrial arrhythmias and embolic complications occur much more frequently in comparison to permanent atrial or sequential pacing. He-modynamic disturbances caused by ventriculoatrial conduction (VAC) are thought to be responsible for those complications. The aim of this study was to compare the left atrial size and its wall motion in three groups of patients with sick sinus syndrome. Group 1: 58 patients with VVI pacing and VAC observed (22 males, 36 females, aged 31–86, mean 62.3). Group 2: 43 patients with primary AAI pacing (13 males, 30 females, aged 27–74, mean 57.8). Group 3: 13 patients with AAI or DDD replacing the primary VVI mode due to pacemaker syndrome and/or heart failure, all with VAC present during VVI pacing (7 males, 6 females, aged 26–80, mean 59.8). Two-dimensional/M-mode echocardiography was performed in all these patients. In group 1 mean diastolic as well as mean systolic atrial diameters were significantly greater (p < 0.005) and wall motion significantly smaller (p < 0.005) in comparison to the other groups. Left atrial wall motion amounted to only 7.4% of the mean diastolic diameter in this group. Mean left atrial diastolic and systolic diameters and wall motion in patients with pacemakers preserving atrioventricular synchrony (group 2 and group 3) were almost identical and wall motion amounted to about 22% of the diastolic diameter in both these groups. We conclude that ventriculoatrial conduction leads to significant enlargement of left atrium and to the atrial wall-motion decrease. This predisposes to arrhythmias and embolic complications. Changes in atrial size and performance seem to be reversible with restoration of the physiological atrioventricular synchrony.     

QT Dynamics and the Risk of Sudden Arrhythmic Cardiac Death in Ischemic Heart Disease

The relationship between altered QT dynamics and the risk of sudden arrhythmic death has not been established so far. This article describes the behavior of QT dynamics assessed in a patient with ischemic heart disease after two documented cardiac arrests due to sustained ventricular arrhythmia. (PACE 2004; 27[Pt. I]:827–828)     

Sulfonated analogues of cyclolinopeptide A Synthesis,immunosuppressive activity and CD studies

Linear and cyclic analogues of cyclolinopeptide A (CLA) in which one or both phenylalanine residues in fragment Pro⁶-Pro⁷-Phe⁸-Phe⁹ were substituted by their sulfonated derivatives have been synthesized by SPPS method and cyclization with the BOP reagent. The peptides were examined for their immunosuppressive activity in the humoral and cellular immune response by PFC and DTH tests. All of the analogues retain some immunosuppressive activity of native CLA. Their CD spectra confirm that the optical activity of aromatic residues in CLA depends on their position in the peptide chain. Only the residue in position 8 seems to be optically active. CD spectrum of the cyclic analogue modified in position 9 is very similar to that of native CLA which correlates with its high biological activity. The chiroptical properties of the p-sulfonated Phe-residue are established. © Munksgaard 1997.     

Conformational modification of the PRP-hexapeptide by a direct covalent attachment of aromatic side chain groups

PRP-hexapeptide possessing the azo-bridge between Tyr¹ and Phe⁵ residues, called azo-PRP-hexapeptide: Tyr-Val-Pro-Leu-Phe-Pro, was synthesized and tested for immunoregulatory activity. High biological activity of the synthesized azo-PRP-hexapeptide suggests that the biologically active conformation of PRP-hexapeptide must be such that both aromatic rings (Tyr and Phe) are apparently close to each other.