Study of the Antihypertensive Peptides Derived from Alpha-Lactalbumin Hydrolysate after Simulation of Digestion
Alpha-lactalbumin is a whey protein that is a cheese-making industrial residue of high biological value. The antihypertensive capacity of three peptides obtained from the simulated gastrointestinal digestion of alpha-lactalbumin hydrolysates was studied. The alpha-lactalbumin hydrolysis was performe...
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| Formato: | Articulo |
| Lenguaje: | Inglés |
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2022
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| Acceso en línea: | http://sedici.unlp.edu.ar/handle/10915/156960 |
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I19-R120-10915-156960 |
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I19-R120-10915-1569602023-08-28T20:06:59Z http://sedici.unlp.edu.ar/handle/10915/156960 Study of the Antihypertensive Peptides Derived from Alpha-Lactalbumin Hydrolysate after Simulation of Digestion Alba, Antonella Báez, Jessica Fernández Fernández, Adriana Maite Nardo, Agustina Estefanía Añón, María Cristina Medrano, Alejandra Paulino, Margot 2022 2023-08-28T14:44:44Z en Ciencias Exactas Biología antihypertensive peptides molecular dynamics simulations simulated digestion Alpha-lactalbumin is a whey protein that is a cheese-making industrial residue of high biological value. The antihypertensive capacity of three peptides obtained from the simulated gastrointestinal digestion of alpha-lactalbumin hydrolysates was studied. The alpha-lactalbumin hydrolysis was performed using the Alcalase enzyme and was subsequently subjected to a simulated digestion process using pepsin and pancreatin enzymes to mimic digestion conditions. The peptides were identified from a RP-HPLC fractionation of the digest and subsequent identification by mass spectrometry analysis. Three peptides from the alpha-lactalbumin sequence were obtained: IWCKDDQNPH (P1), KFLDDDLTDDIM (P2), and DKFLDDDLTDDIM (P3). The in vitro antihypertensive activity of the peptides was determined by studying the inhibition of the angiotensin-converting enzyme, with P1 being the only peptide with antihypertensive activity detected by this methodology (IC₅₀ = 3.91 ± 0.2 mg/mL). In order to correlate the structural (molecular dynamics simulations) and physicochemical properties with potential mechanisms of antihypertensive capacity, in silico methods were performed. The peptides P1, P2, and P3 had a negative global charge and were hydrophilic. After molecular modeling, the peptide structures were submitted to a refinement based on an energy minimization and further molecular dynamics simulation to assess their global size and conformational space. After a 50-nanosecond simulation, the global structures, solvated and immersed in an ionic water solution similar to that of blood, were studied in their solvent-accessible surfaces. A secondary structure (alpha-helix) was observed in the P1 peptide, but in general, all peptides showed an extended folding. The surfaces were charge code colored and in a visual inspection it could be conjectured that all of them exposed the charge, mainly a negative charge, to the solvent surface, in agreement with the GRAVY index, which was also evaluated. In conclusion, the structure and amino acid composition of peptide 1 assessed by in silico studies agrees with the antihypertensive activity obtained by the in vitro study. Centro de Investigación y Desarrollo en Criotecnología de Alimentos Articulo Articulo http://creativecommons.org/licenses/by/4.0/ Creative Commons Attribution 4.0 International (CC BY 4.0) application/pdf |
| institution |
Universidad Nacional de La Plata |
| institution_str |
I-19 |
| repository_str |
R-120 |
| collection |
SEDICI (UNLP) |
| language |
Inglés |
| topic |
Ciencias Exactas Biología antihypertensive peptides molecular dynamics simulations simulated digestion |
| spellingShingle |
Ciencias Exactas Biología antihypertensive peptides molecular dynamics simulations simulated digestion Alba, Antonella Báez, Jessica Fernández Fernández, Adriana Maite Nardo, Agustina Estefanía Añón, María Cristina Medrano, Alejandra Paulino, Margot Study of the Antihypertensive Peptides Derived from Alpha-Lactalbumin Hydrolysate after Simulation of Digestion |
| topic_facet |
Ciencias Exactas Biología antihypertensive peptides molecular dynamics simulations simulated digestion |
| description |
Alpha-lactalbumin is a whey protein that is a cheese-making industrial residue of high biological value. The antihypertensive capacity of three peptides obtained from the simulated gastrointestinal digestion of alpha-lactalbumin hydrolysates was studied. The alpha-lactalbumin hydrolysis was performed using the Alcalase enzyme and was subsequently subjected to a simulated digestion process using pepsin and pancreatin enzymes to mimic digestion conditions. The peptides were identified from a RP-HPLC fractionation of the digest and subsequent identification by mass spectrometry analysis. Three peptides from the alpha-lactalbumin sequence were obtained: IWCKDDQNPH (P1), KFLDDDLTDDIM (P2), and DKFLDDDLTDDIM (P3). The in vitro antihypertensive activity of the peptides was determined by studying the inhibition of the angiotensin-converting enzyme, with P1 being the only peptide with antihypertensive activity detected by this methodology (IC₅₀ = 3.91 ± 0.2 mg/mL). In order to correlate the structural (molecular dynamics simulations) and physicochemical properties with potential mechanisms of antihypertensive capacity, in silico methods were performed. The peptides P1, P2, and P3 had a negative global charge and were hydrophilic. After molecular modeling, the peptide structures were submitted to a refinement based on an energy minimization and further molecular dynamics simulation to assess their global size and conformational space. After a 50-nanosecond simulation, the global structures, solvated and immersed in an ionic water solution similar to that of blood, were studied in their solvent-accessible surfaces. A secondary structure (alpha-helix) was observed in the P1 peptide, but in general, all peptides showed an extended folding. The surfaces were charge code colored and in a visual inspection it could be conjectured that all of them exposed the charge, mainly a negative charge, to the solvent surface, in agreement with the GRAVY index, which was also evaluated. In conclusion, the structure and amino acid composition of peptide 1 assessed by in silico studies agrees with the antihypertensive activity obtained by the in vitro study. |
| format |
Articulo Articulo |
| author |
Alba, Antonella Báez, Jessica Fernández Fernández, Adriana Maite Nardo, Agustina Estefanía Añón, María Cristina Medrano, Alejandra Paulino, Margot |
| author_facet |
Alba, Antonella Báez, Jessica Fernández Fernández, Adriana Maite Nardo, Agustina Estefanía Añón, María Cristina Medrano, Alejandra Paulino, Margot |
| author_sort |
Alba, Antonella |
| title |
Study of the Antihypertensive Peptides Derived from Alpha-Lactalbumin Hydrolysate after Simulation of Digestion |
| title_short |
Study of the Antihypertensive Peptides Derived from Alpha-Lactalbumin Hydrolysate after Simulation of Digestion |
| title_full |
Study of the Antihypertensive Peptides Derived from Alpha-Lactalbumin Hydrolysate after Simulation of Digestion |
| title_fullStr |
Study of the Antihypertensive Peptides Derived from Alpha-Lactalbumin Hydrolysate after Simulation of Digestion |
| title_full_unstemmed |
Study of the Antihypertensive Peptides Derived from Alpha-Lactalbumin Hydrolysate after Simulation of Digestion |
| title_sort |
study of the antihypertensive peptides derived from alpha-lactalbumin hydrolysate after simulation of digestion |
| publishDate |
2022 |
| url |
http://sedici.unlp.edu.ar/handle/10915/156960 |
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