Effects of the substitution of amino acid residues, through chemical synthesis, on the conformation and activity of antimicrobial peptides
<p><em>Antimicrobial peptides make up an assorted group of molecules which contain from 12 to 50 amino acid residues and which may be produced by microorganisms, plants and animals. From the discovery that these biomolecules are lethal to bacteria, inhibiting the pathogenic organism’s gr...
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| Format: | Article |
| Language: | English |
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Universidade Federal de Mato Grosso do Sul
2012-06-01
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| Series: | Orbital: The Electronic Journal of Chemistry |
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| Online Access: | http://orbital.ufms.br/index.php/Chemistry/article/view/372 |
| _version_ | 1818976853803663360 |
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| author | Regina C. Adão Victor Hugo O. Munhoz Bianca Matos Oliveira Mendes Jarbas M. Resende Dorila Piló-Veloso |
| author_facet | Regina C. Adão Victor Hugo O. Munhoz Bianca Matos Oliveira Mendes Jarbas M. Resende Dorila Piló-Veloso |
| author_sort | Regina C. Adão |
| collection | DOAJ |
| description | <p><em>Antimicrobial peptides make up an assorted group of molecules which contain from 12 to 50 amino acid residues and which may be produced by microorganisms, plants and animals. From the discovery that these biomolecules are lethal to bacteria, inhibiting the pathogenic organism’s growth, and are also related to innate and adapted defense mechanisms, the investigation of such molecules came to be an emergent research field, in which more than 1800 antimicrobial peptides have so far been discovered throughout the last three decades. These molecules are potential representatives of a new generation of antibiotic agents and the main motivation for such use is their activity against a wide variety of pathogens, including Gram-positive and Gram-negative bacteria as well as fungi and viruses. An important class of comprising some of these peptides may be found in anurans, from which it has been isolated, a considerable number of antimicrobial peptides with diverse sequences and structures, including linear and dimeric ones. In this work monomeric chains (CH1 e CH2) of the heterodimeric antimicrobial peptide distinctin (isolated in 1999 from Phyllomedusa distincta anurans), as well as its mutated monomers (CH1-S and CH2-S) and the heterodimer itself were synthesized. The distinctin is the peptide with two chains of different sequences (Table 1) bound each other by disulfide bond from the cystein residues constituting the heterodimer. To investigate the effects on the biological activity by amino acids substitution at normal distinctin CH1 and CH2 chains, both were synthesized as well as their similar chains (CH1-S and CH2-S) in which the cystein (Fig.1 <strong>a</strong>) residues of each chain were changed by serin residues (Fig. 1 <strong>b</strong>). The new chains were named mutants. The synthesis was carried out in solid phase, using Fmoc strategy. The heterodimer distinctin was obtained from CH1 and CH2 chains coupling through cystein residues air oxidation. The results from HPLC purification of the peptides showed different retention times of the normal and mutants chains. In the interaction with biomimetic membranes analyzed by ITC, the CH1, CH2, and distinctin showed unlike behavior. The set of results suggest that the action mechanism of these antimicrobial peptides on the bacterial membrane is intrinsically related with the amino acids sequence and the structural conformation, according to the mechanisms proposed in the literature.</em></p> |
| first_indexed | 2024-12-20T16:18:27Z |
| format | Article |
| id | doaj.art-8aa750b9112c492d829087ecc33c2ed9 |
| institution | Directory Open Access Journal |
| issn | 1984-6428 |
| language | English |
| last_indexed | 2024-12-20T16:18:27Z |
| publishDate | 2012-06-01 |
| publisher | Universidade Federal de Mato Grosso do Sul |
| record_format | Article |
| series | Orbital: The Electronic Journal of Chemistry |
| spelling | doaj.art-8aa750b9112c492d829087ecc33c2ed92022-12-21T19:33:43ZengUniversidade Federal de Mato Grosso do SulOrbital: The Electronic Journal of Chemistry1984-64282012-06-0141697110.17807/orbital.v4i1.372142Effects of the substitution of amino acid residues, through chemical synthesis, on the conformation and activity of antimicrobial peptidesRegina C. Adão0Victor Hugo O. Munhoz1Bianca Matos Oliveira Mendes2Jarbas M. Resende3Dorila Piló-Veloso4Departamento de Química, Universidade Federal de Minas Gerais (UFMG)Departamento de Química, Universidade Federal de Minas Gerais (UFMG)Departamento de Química, Universidade Federal de Minas Gerais (UFMG)Departamento de Química, Universidade Federal de Minas Gerais (UFMG)Departamento de Química, Universidade Federal de Minas Gerais (UFMG)<p><em>Antimicrobial peptides make up an assorted group of molecules which contain from 12 to 50 amino acid residues and which may be produced by microorganisms, plants and animals. From the discovery that these biomolecules are lethal to bacteria, inhibiting the pathogenic organism’s growth, and are also related to innate and adapted defense mechanisms, the investigation of such molecules came to be an emergent research field, in which more than 1800 antimicrobial peptides have so far been discovered throughout the last three decades. These molecules are potential representatives of a new generation of antibiotic agents and the main motivation for such use is their activity against a wide variety of pathogens, including Gram-positive and Gram-negative bacteria as well as fungi and viruses. An important class of comprising some of these peptides may be found in anurans, from which it has been isolated, a considerable number of antimicrobial peptides with diverse sequences and structures, including linear and dimeric ones. In this work monomeric chains (CH1 e CH2) of the heterodimeric antimicrobial peptide distinctin (isolated in 1999 from Phyllomedusa distincta anurans), as well as its mutated monomers (CH1-S and CH2-S) and the heterodimer itself were synthesized. The distinctin is the peptide with two chains of different sequences (Table 1) bound each other by disulfide bond from the cystein residues constituting the heterodimer. To investigate the effects on the biological activity by amino acids substitution at normal distinctin CH1 and CH2 chains, both were synthesized as well as their similar chains (CH1-S and CH2-S) in which the cystein (Fig.1 <strong>a</strong>) residues of each chain were changed by serin residues (Fig. 1 <strong>b</strong>). The new chains were named mutants. The synthesis was carried out in solid phase, using Fmoc strategy. The heterodimer distinctin was obtained from CH1 and CH2 chains coupling through cystein residues air oxidation. The results from HPLC purification of the peptides showed different retention times of the normal and mutants chains. In the interaction with biomimetic membranes analyzed by ITC, the CH1, CH2, and distinctin showed unlike behavior. The set of results suggest that the action mechanism of these antimicrobial peptides on the bacterial membrane is intrinsically related with the amino acids sequence and the structural conformation, according to the mechanisms proposed in the literature.</em></p>http://orbital.ufms.br/index.php/Chemistry/article/view/372peptidessynthesisfmoccysteineserin |
| spellingShingle | Regina C. Adão Victor Hugo O. Munhoz Bianca Matos Oliveira Mendes Jarbas M. Resende Dorila Piló-Veloso Effects of the substitution of amino acid residues, through chemical synthesis, on the conformation and activity of antimicrobial peptides Orbital: The Electronic Journal of Chemistry peptides synthesis fmoc cysteine serin |
| title | Effects of the substitution of amino acid residues, through chemical synthesis, on the conformation and activity of antimicrobial peptides |
| title_full | Effects of the substitution of amino acid residues, through chemical synthesis, on the conformation and activity of antimicrobial peptides |
| title_fullStr | Effects of the substitution of amino acid residues, through chemical synthesis, on the conformation and activity of antimicrobial peptides |
| title_full_unstemmed | Effects of the substitution of amino acid residues, through chemical synthesis, on the conformation and activity of antimicrobial peptides |
| title_short | Effects of the substitution of amino acid residues, through chemical synthesis, on the conformation and activity of antimicrobial peptides |
| title_sort | effects of the substitution of amino acid residues through chemical synthesis on the conformation and activity of antimicrobial peptides |
| topic | peptides synthesis fmoc cysteine serin |
| url | http://orbital.ufms.br/index.php/Chemistry/article/view/372 |
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