Biomedical subjects

A Kluczyk

Publications and source records attributed to A Kluczyk.

10 recordsLinked to original sources

PubMed2006

Drug evolution concept in drug design: 2. Chimera method.

The drug evolution method represents a novel approach towards efficient rational drug design by implementing the drug evolution concept to the creation and development of general chemical libraries with the purpose of allowing the identification of drug candidates with improved odds and lesser costs than the traditional drug design strategies. As another example of successful translation of the biological evolution into chemical evolution, the chimera method comprises the grafting of selected building blocks, identified through a basic search within a drug library, onto the same substitution sites on a rationally chosen scaffold. The method allows the creation of a library containing both drugs and prospective drug candidates without any priorly required knowledge on the pursued disease or molecular target. Two libraries having scaffolds derived from para-aminobenzoic acid and salicylic acid have exemplified the application of the chimera method. The validation of the method has been achieved through the high number of recognized drugs within the library, which exhibit in the same time a wide variety of therapeutic activities and interact with a broad spectrum of molecular targets. The drug-enriched chimera libraries are expected to provide a highly efficient access to novel drug candidates whose unspecified therapeutic effects should be further revealed through high-throughput screening.

4-Aminobenzoic Acid↗

PubMed2005

The peptide molecular links between the central nervous and the immune systems.

The central nervous system (CNS) and the immune system were for many years considered as two autonomous systems. Now, the reciprocal connections between them are generally recognized and very well documented. The links are realized mainly by various immuno- and neuropeptides. In the review the influence of the following immunopeptides on CNS is presented: tuftsin, thymulin, thymopoietin and thymopentin, thymosins, and thymic humoral factor. On the other side, the activity in the immune system of such neuropeptides as substance P, neurotensin, some neurokinins, enkephalins, and endorphins is discussed.

Animals↗

PubMed2000

The "two-headed" peptide inhibitors of interleukin-1 action.

Two peptide fragments of IL-1 family proteins, ITGSE and VTKFYF compete with IL-1 for the cellular receptor. We synthesized a series of peptides composed of the sequences ITGSE and VTKFYK bound directly to each other or connected by such linkers as (Gly)(n), L- and D-Pro residues, Glu and Lys residues (with peptide bond formed by main amino and carboxy groups or by side chain groups), and beta-alanine and its homologues. Peptide IX with a gamma-Glu linker was the most potent inhibitor of IL-1 action. It was twice as potent as both of the peptides indicated.

Animals↗

PubMed1999

Tuftsin: on the 30-year anniversary of Victor Najjar's discovery.

After a short description of the results of Victor Najjar's research on tuftsin and of the discoveries done by other authors in the early stage of tuftsin investigation, the current state of work on tuftsin is presented, based mainly on the literature published in the years 1984-1997. The presentation follows this order: the occurrence of tuftsin and retro-tuftsin sequences in proteins, their synthesis and biology, the antigenic properties of tuftsin, its influence on phagocytic cells, and other biologic activities of tuftsin, including antimicrobial, antiviral, antitumor and central effects, and the search for tuftsin superactive analogs.

Amino Acid Sequence↗

PubMed1998

Anti-IL-1 activity of peptide fragments of IL-1 family proteins.

A series of peptides containing retro-tuftsin- and tuftsin-like motifs from IL-1 proteins inhibits IL-1-induced IL-2 production and reduces the humoral immune response, thus supporting our hypothesis that tuftsin (Thr-Lys-Pro-Arg)-IL-1 competition depends on the presence of such motifs in IL-1 proteins. Some other peptides from regions of IL-1 responsible for receptor binding were also active, with peptide Ile-Thr-Gly-Ser-Glu (III) from IL-1alpha (residues 98-102), not only strongly affecting IL-2 production, but also suppressing the immune response; the analogue of hexapeptide Val-Thr-Lys-Phe-Tyr-Phe from the C-terminal part of IL-lra, with Lys replaced by Asp, was as efficient as Val-Thr-Lys-Phe-Tyr-Phe with respect to IL-1 competition.

Amino Acid Sequence↗

PubMed1997

Immunomodulatory activity of oligopeptides related to interleukin 1 receptor antagonist sequence.

We examined the immunomodulatory properties of peptides from interleukin 1 receptor antagonist (IL-1Ra) with regard to the humoral (plaqueforming cells-PFC) and cellular (delayed type hypersensitivity-DTH) immune response and GvH reaction. It was found that peptide RKSSK (II) from the N-terminal part of IL-1Ra, although inactive with regard to the inhibition of IL-1-IL-1 receptor interaction, reduces immune response in a manner similar to cyclosporin A (DTH, PFC in vivo). Peptide GRKSSK (III) was even more potent, whereas peptides from respective fragment of mouse IL-1Ra were weaker immunosuppressants than II. Peptide VTKFYF (VII) from the C-terminal part of IL-1Ra, very active as IL-1 inhibitor, and its analog VIII with Asp residue, characteristic for IL-1, instead of Lys from IL-1Ra, showed only limited activity despite the previously observed competition with IL-1 for the cellular receptor. Thus, no correlation between the inhibitory and immunomodulatory properties of peptides derived from IL-1Ra was observed.

Adjuvants, Immunologic↗

PubMed1995

The immunomodulatory diversity of the proteins of the transforming growth factor beta (TGF beta) family.

The examination of immunomodulatory properties of oligopeptides derived from two exposed loops (containing thymopentin-like and tuftsin-like sequences, respectively) of the proteins belonging to TGF beta family suggests that the particular species of the TGF beta family should differ distinctly in their influence on the immune response. According to our results obtained from three TGF beta species of mammals, TGF beta 2 should be a strong immunosuppressor, whereas for TGF beta 3 the immunostimulative potency is more probable. TGF beta 1 species would possess both immunosuppressive and immunostimulative potency, residing in two different loops of the protein. The results obtained also suggest that chicken TGF beta 4 should be associated with immunostimulative effects and xenopus TGF beta 5 with immunosuppressive ones.

Adjuvants, Immunologic↗

PubMed1994

Immunosuppressive activity of analogs of tripeptide Lys-Arg-Pro with D-amino acid residues.

Synthesis of four analogs, containing D-amino acid residues, of the tripeptide immunosuppressor Lys-Arg-Pro is described. In addition, acetyl and amide derivatives of this peptide were synthesized. Biological effects of all peptides were studied using a delayed type hypersensitivity (DTH) test. It was found that incorporation of D-amino acid residues in definite positions of the peptide chain gives the substances with immunosuppressive activity. A strong immunosuppressive activity was observed also for all-D-analogs (D-Lys-D-Arg-D-Pro).

Amino Acid Sequence↗

PubMedDate not supplied

A hexapeptide VTKFYF from C-terminal part of interleukin-1 receptor antagonist, an inhibitor of IL-1-IL-1 receptor interaction.

In order to find the low-molecular-weight interleukin-1 (IL-1) inhibitors we synthesized a series of peptides, derived from three regions of interleukin-1 receptor antagonist (IL-1ra): N-terminal (residues 5-9), central (90-98) and C-terminal (143-148). The decision was based on the thorough analysis of structural and functional properties of IL-1 proteins and the resemblance of some fragments of IL-1ra to well-known immunomodulators, like thymopentin and tuftsin. The competition between our peptides and IL-1 was measured as the inhibition of IL-1 induced IL-2 production in LBRM/CTLL cell line system. The activity of tuftsin (TKPR), a peptide immunomodulator derived from IgG molecule, was also examined. All peptides presented some activity, although the most interesting results (when the range of activity and dose-dependence were taken into account) were obtained for tuftsin and peptide VTKFYF from the C-terminal part of IL-1ra, which is in agreement with the latest reports on the structure of IL-1ra-receptor complex.

Cell Line↗

PubMedDate not supplied

The search for inhibitors of interleukin-1 based on the sequence of interleukin-1 receptor antagonist.

In order to find the low-molecular-weight interleukin-1 (IL-1) inhibitors, we synthesised a series of peptides, derived from three regions of interleukin-1 receptor antagonist (IL-1ra): N-terminal (residues 5-9), central (90-98) and C-terminal (143-148). The decision was based on the thorough analysis of structural and functional properties of IL-1 proteins and the resemblance of some fragments of IL-1ra to well-known immunomodulators, like thymopentin and tuftsin. The competition between our peptides and IL-1 were measured as the inhibition of IL-1 induced IL-2 production in LBRM/CTLL cell line system. All peptides presented some activity, although the most interesting results (when the range of activity and dose-dependence were taken into account) were obtained for tuftsin and peptide VTKFYF from the C-terminal part of IL-1ra.

Amino Acid Sequence↗