The peptides of alpha-aminosuberic acid II. Synthesis of deamino-dicarba-eel-calcitonin sequence 1-9.

The paper describes the synthesis of Asu6-octapeptide derivatives by condensing two alternative pentapeptide fragments with Asu-containing tripeptides. After partial deprotection these linear peptides compounds are subject to cyclization experiments aimed to give the N-terminal [1-9] sequence of deamino-dicarba-eel calcitonin. This is a key substance for the semi-synthesis of the respective analogues of eel calcitonin.

The peptides of alpha-aminosuberic acid I. New intermediates for synthetic studies.

The paper describes the synthesis of alpha-aminosuberic acid derivatives suitable for the synthesis of peptides. These include Z-, Boc- and Fmoc-protection on the alpha-amino group, benzyl ester, Boc-hydrazide and Z-hydrazide as well as the free carboxylic function in the side chain, and methyl ester, benzyl ester or free alpha-carboxylic group. Their use is demonstrated on the synthesis of the respective derivatives of Asu-Val-Leu. The enzyme catalyzed reaction was successfully used both as a route to L-Asu from the D,L-compound as well as for the direct synthesis of the optically active tripeptide derivative from the Z-D,L-Asu-OH.

Impact of HIV infection on tuberculosis.

Tuberculosis is increasing in prevalence in many countries and is now the leading infectious cause of death world wide, being responsible for three million deaths annually. Infection with HIV, likewise increasing in prevalence, has emerged as the most important predisposing factor for developing overt tuberculosis in people co-infected with Mycobacterium tuberculosis. Owing to the widespread geographical overlap of these two infections, it is estimated that in 1999, HIV related tuberculosis will reach one million cases and will cause 30% of the expected 2.5 million AIDS related deaths. Tuberculosis in HIV infected individuals may have unusual clinical features and can cause diagnostic difficulties. Despite the effectiveness of modern short course treatment, the mortality of HIV related tuberculosis during and after treatment remains high, and this may be due to other HIV related infections. The "cursed duet" of infection with both HIV and M tuberculosis is generating a threat to human health of unparalleled proportions which, if not taken seriously by health workers and decision makers, could become totally unmanageable.

Resolution of DL-2-aminosuberic acid via protease-catalyzed ester hydrolysis.

Papain-catalyzed regioselective cleavage of alpha-methyl ester in Z-DL-Asu(OMe)-OMe leads to Z-L-Asu(OMe)-OH and Z-D-Asu(OMe)-OMe. Subsequent saponifications yield Z-L-Asu-OH and Z-D-Asu-OH. The enzymatic alpha-ester hydrolysis was also achieved by subtilisin BPN' in organic solvent with low water content.

Comparative multiple synthesis of fifty linear peptides: evaluation of cotton carrier vs. T bag-benzhydrylamine resin.

Parallel simultaneous synthesis of fifty linear peptides has been carried out in order to compare in detail two promising methodologies of simultaneous multiple peptide synthesis (SMPS): the "T bag" method, utilizing 4-methyl-benzhydrylamine resin (MeBHA), and synthesis on derivatized Fmoc-Gly-O-cotton fabric strips. The basic set of experiments, which utilizes identical Fmoc/Bu(t) strategy for both approaches, shows that the peptides synthesized on cotton are superior in purity to those synthesized using T bags. In experiments utilizing Boc/Bzl strategy in T bags, the purities of peptides were higher than in the case of peptides synthesized in T bags by Fmoc/Bu(t) strategy, and comparable with the purities achieved in synthesis performed on cotton. The lower yields on cotton are caused by mechanical losses in the given experimental arrangement.

Interaction of Z-4,4-bis(4-ethylphenyl)-2,3-dibromo-2-butenoic acid with aminotransferases: changes in absorption and circular dichroism spectra.

The influence of Z-4,4-bis(4-ethylphenyl)-2,3-dibromo-2-butenoic acid, the compound originally synthetized as a cytostatic edikron and showing inhibitory effect on several pyridoxal enzymes, on absorption and circular dichroism spectra of alanine and aspartate aminotransferases (ALT, AST) in the region of coenzyme absorption characteristics was studied. In the case of AST, the compound decreased absorption and CD maxima at 360 nm, which represents the active form of the enzyme, but it did not seem to prevent formation of the pyridoxamine form of the enzyme, produced in the presence of L-aspartate. Edikron caused insignificant spectral changes of ALT, but it partially denatured the enzyme. Circular dichroism measurement of both enzymes uncovered some effects of edikron at 250-300 nm, which suggests conformational changes in the aromatic amino acids of the apoenzymes due to the compound studied.