Abstract
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 α-helical structure, and to inhibit the growth of microorganisms at concentrations as low as 1μM. Hs02, a novel sixteen residue long internal peptide (KWAVRIIRKFIKGFIS-NH2) derived from the unconventional myosin 1h protein, was further investigated in its capacity to inhibit lipopolysaccharide-induced release of TNF-α in murine macrophages. Hs02 presented potent anti-inflammatory activity, inhibiting the release of TNF-α in LPS-primed cells at the lowest assayed concentration, 0.1 μM. 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.
Highlights
Sometimes, Art may offer better ways than Hard Sciences to find truth and understand reality
We report the uncovering as well as the biochemical and biophysical evaluations of four new representative peptides derived from the internal sequences of human proteins, called Hs IAPs, or Homo sapiens Intragenic Antimicrobial Peptides
Here we demonstrate that the novel Hs IAPs disturb the main phase transition of model membranes, fold into amphiphilic α-helical segments upon binding to model membranes and display distinct antimicrobial activities against Grampositive, and -negative bacteria as well as yeasts and filamentous fungi, and one of these IAPs—Hs02 (KWAVRIIRKFIKGFIS-NH2)—derived from the unconventional myosin 1h protein (NP_001094891.3), is a potential inhibitor of lipopolysaccharide-induced release of pro-inflammatory mediators in murine macrophages
Summary
Art may offer better ways than Hard Sciences to find truth and understand reality. Just some of them: a) as a linear biopolymer, product of the translation of RNA molecules by ribosomes in the cytoplasm; b) as unique sequences of covalently linked amino acid residues that serve as substrate for enzymes that catalyze various post-translation modifications; c) as a set of peptide building blocks, secondary structures, domains that are determinant to their final tridimensional folding and mature topology; d) or as molecules exposed to large—occasionally dramatic—internal motions and conformational changes induced by solvents, small ligands, proteins and other macromolecules in order to perform their biological functions under certain physicochemical conditions
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