RESUMO
Review is devoted to studying the interaction muramyl peptides with protein components of immune system cells. Systems analysis of published results may be useful to select not only the strategy to further explore the function of this class of glycopeptides, but their use in clinical practice.
Assuntos
Acetilmuramil-Alanil-Isoglutamina/farmacologia , Adjuvantes Imunológicos/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Transdução de Sinais/efeitos dos fármacos , Imunidade Adaptativa/efeitos dos fármacos , Imunidade Adaptativa/imunologia , Animais , Linhagem Celular , Humanos , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/imunologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Proteína Adaptadora de Sinalização NOD2/metabolismo , Mapeamento de Interação de Proteínas , Transdução de Sinais/imunologia , Receptores Toll-Like/metabolismoRESUMO
The structure-function relationships in a series of synthetic glucosaminylmuramyl peptides--glycopeptide adjuvants of the bacterial origin--have been investigated. Modification of the N-acetylglucosaminyl-(beta 1-4)-N-acetylmuramyl-L-alanyl-D-isoglutamine (GMDP) molecule affects its adjuvant and pyrogenic activity in vivo. GMDP is shown to readily stimulate the synthesis of the IgG2a and IgG3 of the immunoglobulin subclasses upon the secondary immune response to the protein antigen. The adjuvant effect correlates with the comitogenic test of the reaction of splenocytes blast-transformation in the presence of B-cell mitogen. No direct dependence has been revealed between the level of the glycopeptides adjuvant action and their effect on the IL-1 production by macrophages.
Assuntos
Acetilmuramil-Alanil-Isoglutamina/análogos & derivados , Acetilmuramil-Alanil-Isoglutamina/química , Adjuvantes Imunológicos , Acetilmuramil-Alanil-Isoglutamina/farmacologia , Animais , Feminino , Soros Imunes , Imunoglobulina G/análise , Imunoglobulina G/biossíntese , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Relação Estrutura-AtividadeRESUMO
In order to increase immunogenicity of the peptide (NANP)3, we have prepared a large set of fully synthetic constructions based on the peptide, glycopeptide adjuvant GMDP and some synthetic carriers. Immunogenicity of these constructions was tested on mice (line C57B1/6) responding to the peptide polymer (NANP)40 without carrier and on mice (line BALB/c) not responding to this antigen. Immunogenic constructions based on synthetic polytuftsin induced as high titres of anti-(NANP)3 antibodies as the standard conjugate KLH--(NANP)3. The chimeric peptide consisting of (NANP)3 and tuftsin dimer induced anti-(NANP)3 antibodies in both lines of mice as well. The GMDP covalent attachment to the immunogenic constructions increased the antipeptide antibodies titre. The results are discussed in terms of an approach to synthetic vaccines.
Assuntos
Antígenos de Protozoários/metabolismo , Peptídeos/imunologia , Plasmodium falciparum/metabolismo , Proteínas de Protozoários , Sequência de Aminoácidos , Animais , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Epitopos/imunologia , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Vacinas Sintéticas/imunologiaRESUMO
Synthetic constructions containing a peptide antigenic determinant (C-terminal peptide 205-213 of the surface VP1 protein of the foot-and-mouth disease virus, O1K strain), glucosaminylmuramayl dipeptide (GMDP), and polyionic synthetic carriers were prepared. The polymerized peptide and peptide-BSA conjugates were synthesized as well. Among the constructions obtained only peptide-BSA conjugate proved to be highly immunogenic. Application of synthetic constructions to design immunogenic complexes is discussed.
Assuntos
Antígenos Virais/imunologia , Aphthovirus/imunologia , Capsídeo/imunologia , Peptídeos/imunologia , Sequência de Aminoácidos , Antígenos Virais/síntese química , Capsídeo/síntese química , Proteínas do Capsídeo , Ensaio de Imunoadsorção Enzimática , Dados de Sequência Molecular , Peptídeos/síntese química , Soroalbumina Bovina/química , Soroalbumina Bovina/imunologia , Vacinas Sintéticas/síntese química , Vacinas Virais/síntese químicaRESUMO
A conformational behaviour of pepsin depending on pH and temperature was studied by circular dichroism, differential UV-spectroscopy, calorimetry and enzymatic hydrolysis kinetics. A subtile conformational transition of the enzyme accompanied by changes in the physico-chemical and enzymatic properties of the protein was observed within the temperature interval of 15--40 degrees and within the pH range of 1,1--5,6. The range of pepsin heat denaturation was studied. A diagram of pepsin conformational states under different values of pH and temperature was built.