Biomedical subjects

J Stehlíková

Publications and source records attributed to J Stehlíková.

At least 19 recordsLinked to original sources

PubMed1993

Specificity mapping of HIV-1 protease by reduced bond inhibitors.

A series of 47 N-truncated reduced bond inhibitors, systematically modified at individual positions (P1, P'1, P'2, P'3, and P'4), were synthesized and used to map the subsite preferences of HIV-1 protease. The tight binding inhibitor of HIV-1 protease t-butoxycarbonyl-Phe-[CH2NH]Phe-Glu-Phe-NH2 (Ki = 0.2 nM) was chosen as the parent structure for further modifications. The P'2 glutamic acid was found to fit well into the S'2 subsite of the protease. The conformational restriction of any phenylalanine residue or saturation of more than one phenylalanine side chain in P'1 or P'3 lead is to a large Ki increase. Introduction of tyrosine in the P1 position improves the binding by an order of magnitude. The S'4 subsite of the protease was shown to accommodate large structural changes in the inhibitor at this position. Therefore P'4 may serve as an ideal region for further modification in order to improve bioavailability of this type of compound. An improved method of direct comparison of tight binding inhibitors with subnanomolar Ki values has been described.

Binding Sites↗

PubMed1993

[Immunologic findings in children with abnormal reactions after vaccination].

In a group of 89 children with abnormal reactions after administration of the mixed vaccine against diphtheria, tetanus and whooping cough, after the mixed vaccine against diphtheria and tetanus, the live measles vaccine and oral poliovaccine, a detailed analysis was made of the case-history, and basic parameters of cellular and humoral immunity were examined. In these children the intensity of post-vaccination reactions was beyond the range of accepted criteria of mild and medium reactions or complications. In 17.3% of the children with an abnormal reaction after the mixed vaccine against diphtheria, tetanus and whooping cough a reduced IgA level was proved, while in the control group a reduced level was found only in 3.3%. 50% of the children who developed an abnormal reaction after the oral poliovaccine and the mixed vaccine against diphtheria, tetanus and whooping cough and at the same time some relative suffered from clinical signs of atopia, a reduced number of E rosettes of lymphocytes was recorded. 80% of the children who developed an abnormal reaction after the measles vaccine and some relative suffered from atopic disease, had low titres of specific antibodies against tetanic toxoid. Evidence was provided that children with certain precisely defined abnormal reactions after vaccination suffered significantly more frequently from reduced immune reactivity than children examined because of a suspected immunity defect.

Antibodies, Bacterial↗

PubMed1992

Reduced-bond tight-binding inhibitors of HIV-1 protease. Fine tuning of the enzyme subsite specificity.

Truncation of a peptide substrate in the N-terminus and replacement of its scissile amide bond with a non-cleavable reduced bond results in a potent inhibitor of HIV-1 protease. A series of such inhibitors has been synthesized, and S2-S3' subsites of the protease binding cleft mapped. The S2 pocket requires bulky Boc or PIV groups, large aromatic Phe residues are preferred in P1 and P1' and Glu in P2'. The S3' pocket prefers Phe over small Ala or Val. Introduction of a Glu residue into the P2' position yields a tight-binding inhibitor of HIV-1 protease, Boc-Phe-[CH2-NH]-Phe-Glu-Phe-OMe, with a subnanomolar inhibition constant. The relevant peptide derived from the same amino acid sequence binds to the protease with a Ki of 110 nM, thus still demonstrating a good fit of the amino acid residues into the protease binding pockets and also the importance of the flexibility of P1-P1' linkage for proper binding. A new type of peptide bond mimetic, N-hydroxylamine -CH2-N(OH)-, has been synthesized. Binding of hydroxylamino inhibitor of HIV-1 protease is further improved with respect to reduced-bond inhibitor.

Amino Acid Sequence↗

PubMed1992

[Immunization against diphtheria and tetanus in children with severe neurological disorders].

In the clinical department of the Institute for Sera and Vaccines 260 children with serious neurological diseases were immunized with Alditeana and Alteana. After immunization an undesirable reaction was recorded in 3.1% of the immunized children. Mostly recurrence or potentiation of clinical manifestations of the basic neurological disease of the child was involved. Investigation of the anamnestic data revealed several serious undesirable reactions after vaccination with Alditepera in a health centre for child patients.

Adolescent↗

PubMed1989