دورية أكاديمية
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Probing human proteins for short encrypted antimicrobial peptides reveals Hs10, a peptide with selective activity for gram-negative bacteria.

التفاصيل البيبلوغرافية
العنوان: Probing human proteins for short encrypted antimicrobial peptides reveals Hs10, a peptide with selective activity for gram-negative bacteria.
المؤلفون: Santos MA; Laboratório de Ressonância Magnética Nuclear, LRMN, Instituto de Química, Universidade de Brasília, Brasília, DF, Brazil; Laboratório de Síntese e Análise de Biomoléculas, LSAB, Instituto de Química, Universidade de Brasília, Brasília, DF, Brazil., Silva FL; Laboratório de Síntese e Análise de Biomoléculas, LSAB, Instituto de Química, Universidade de Brasília, Brasília, DF, Brazil., Lira BOV; Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brasília, DF, Brazil., Cardozo Fh JL; Laboratório de Espectrometria de Massa, LEM, Embrapa Recursos Genéticos e Biotecnologia, Brasília, DF, Brazil., Vasconcelos AG; Núcleo de Pesquisa em Morfologia e Imunologia Aplicada, NuPMIA, Faculdade de Medicina, Campus Universitário Darcy Ribeiro, Universidade de Brasília, Brasília, DF, Brazil., Araujo AR; Núcleo de Pesquisa em Biodiversidade e Biotecnologia, Universidade Federal do Piauí, Parnaíba, PI, Brazil., Murad AM; Laboratório de Espectrometria de Massa, LEM, Embrapa Recursos Genéticos e Biotecnologia, Brasília, DF, Brazil., Garay AV; Laboratório de Biofísica Molecular, Instituto de Biologia, Universidade de Brasília (IB-CEL/UnB), Campus Darcy Ribeiro, Asa Norte, Brasília, DF, Brazil., Freitas SM; Laboratório de Biofísica Molecular, Instituto de Biologia, Universidade de Brasília (IB-CEL/UnB), Campus Darcy Ribeiro, Asa Norte, Brasília, DF, Brazil., Leite JRSA; Núcleo de Pesquisa em Morfologia e Imunologia Aplicada, NuPMIA, Faculdade de Medicina, Campus Universitário Darcy Ribeiro, Universidade de Brasília, Brasília, DF, Brazil., Bloch C Jr; Laboratório de Espectrometria de Massa, LEM, Embrapa Recursos Genéticos e Biotecnologia, Brasília, DF, Brazil., Ramada MHS; Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brasília, DF, Brazil; Programa de Pós-Graduação em Gerontologia, Universidade Católica de Brasília, Brasília, DF, Brazil., de Oliveira AL; Laboratório de Ressonância Magnética Nuclear, LRMN, Instituto de Química, Universidade de Brasília, Brasília, DF, Brazil., Brand GD; Laboratório de Síntese e Análise de Biomoléculas, LSAB, Instituto de Química, Universidade de Brasília, Brasília, DF, Brazil. Electronic address: gdbrand@unb.br.
المصدر: Biochimica et biophysica acta. General subjects [Biochim Biophys Acta Gen Subj] 2023 Jan; Vol. 1867 (1), pp. 130265. Date of Electronic Publication: 2022 Oct 21.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101731726 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-8006 (Electronic) Linking ISSN: 03044165 NLM ISO Abbreviation: Biochim Biophys Acta Gen Subj Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Amsterdam : Elsevier
مواضيع طبية MeSH: Escherichia coli*/metabolism , Anti-Infective Agents*, Humans ; Antimicrobial Peptides ; Lipopolysaccharides/pharmacology ; Proteome ; Gram-Negative Bacteria/metabolism ; Peptides/chemistry
مستخلص: Background: Some cationic and amphiphilic α-helical segments of proteins adsorb to prokaryotic membranes when synthesized as individual polypeptide sequences, resulting in broad and potent antimicrobial activity. However, amphiphilicity, a determinant physicochemical property for peptide-membrane interactions, can also be observed in some β-sheets.
Methods: The software Kamal was used to scan the human reference proteome for short (7-11 amino acid residues) cationic and amphiphilic protein segments with the characteristic periodicity of β-sheets. Some of the uncovered peptides were chemically synthesized, and antimicrobial assays were conducted. Biophysical techniques were used to probe the molecular interaction of one peptide with phospholipid vesicles, lipopolysaccharides (LPS) and the bacterium Escherichia coli.
Results: Thousands of compatible segments were found in human proteins, five were synthesized, and three presented antimicrobial activity in the micromolar range. Hs10, a nonapeptide fragment of the Complement C3 protein, could inhibit only the growth of tested Gram-negative microorganisms, presenting also little cytotoxicity to human fibroblasts. Hs10 interacted with LPS while transitioning from an unstructured segment to a β-sheet and increased the hydrodynamic radius of LPS particles. This peptide also promoted morphological alterations in E. coli cells.
Conclusions: Data presented herein introduce yet another molecular template to probe proteins in search for encrypted membrane-active segments and demonstrates that, using this approach, short peptides with low cytotoxicity and high selectivity to prokaryotic cells might be obtained.
General Significance: This work widens the biotechnological potential of the human proteome as a source of antimicrobial peptides with application in human health.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: Antimicrobial peptides; Kamal; Novel antibiotics; Proteome
المشرفين على المادة: 0 (Antimicrobial Peptides)
0 (Lipopolysaccharides)
0 (Proteome)
0 (Peptides)
0 (Anti-Infective Agents)
تواريخ الأحداث: Date Created: 20221024 Date Completed: 20221116 Latest Revision: 20230224
رمز التحديث: 20231215
DOI: 10.1016/j.bbagen.2022.130265
PMID: 36280021
قاعدة البيانات: MEDLINE
الوصف
تدمد:1872-8006
DOI:10.1016/j.bbagen.2022.130265