Intragenic antimicrobial peptides

Following the treads of our previous works on the unveiling of bioactive peptides encrypted in plant proteins from diverse species, the present manuscript reports the occurrence of four proof-of-concept intragenic antimicrobial peptides in human proteins, named Hs IAPs. These IAPs were prospected us...

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Bibliographic Details
Published in:PloS one 2019-08, Vol.14 (8), p.e0220656
Main Authors: Brand, Guilherme D, Ramada, Marcelo H. S, Manickchand, Júlia R, Correa, Rafael, Ribeiro, Dalila J. S, Santos, Michele A, Vasconcelos, Andreanne G, Abrão, Fernando Y, Prates, Maura V, Murad, André M, Cardozo Fh, José L, Leite, José Roberto S. A, Magalhães, Kelly G, Oliveira, Aline L, Bloch, Carlos
Format: Article
Language:English
Subjects:
Anti-inflammatory agents
Antimicrobial peptides
Bacteria
Calorimetry
Chemical properties
Evaluation
Fungi
Genomics
Health aspects
Human genome
Macrophages
Microorganisms
Mitogens
Muscle proteins
Myosin
Novels
Peptides
Phospholipids
Proteins
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Summary:Following the treads of our previous works on the unveiling of bioactive peptides encrypted in plant proteins from diverse species, the present manuscript reports the occurrence of four proof-of-concept intragenic antimicrobial peptides in human proteins, named Hs IAPs. These IAPs were prospected using the software Kamal, synthesized by solid phase chemistry, and had their interactions with model phospholipid vesicles investigated by differential scanning calorimetry and circular dichroism. Their antimicrobial activity against bacteria, yeasts and filamentous fungi was determined, along with their cytotoxicity towards erythrocytes. Our data demonstrates that Hs IAPs are capable to bind model membranes while attaining [alpha]-helical structure, and to inhibit the growth of microorganisms at concentrations as low as 1[mu]M. Hs02, a novel sixteen residue long internal peptide (KWAVRIIRKFIKGFIS-NH.sub.2) derived from the unconventional myosin 1h protein, was further investigated in its capacity to inhibit lipopolysaccharide-induced release of TNF-[alpha] in murine macrophages. Hs02 presented potent anti-inflammatory activity, inhibiting the release of TNF-[alpha] in LPS-primed cells at the lowest assayed concentration, 0.1 [mu]M. A three-dimensional solution structure of Hs02 bound to DPC micelles was determined by Nuclear Magnetic Resonance. Our work exemplifies how the human genome can be mined for molecules with biotechnological potential in human health and demonstrates that IAPs are actual alternatives to antimicrobial peptides as pharmaceutical agents or in their many other putative applications.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0220656