Influence of D-arg and D-lys on the structure and antibacterial activities of computer-made peptides — ASN Events
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  3. Influence of D-arg and D-lys on the structure and antibacterial activities of computer-made peptides

Influence of D-arg and D-lys on the structure and antibacterial activities of computer-made peptides (#348)

Samilla B Rezende 1 , Elizabete Cândido 1 2 , Lai Yue Angeline Chan 3 , Karen Oshiro 2 , David Craik 3 , Octávio Franco 1 2 4 , Marlon Cardoso 1 2 4
  1. S-Inova, Programa de Pós-Graduação em Biotecnologia, Universidade Católica Dom Bosco, Campo Grande, MS, Brazil
  2. Centro de Análises Proteômicas e Bioquímicas, Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brasília, DF, Brazil
  3. Institute for Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia
  4. Programa de Pós-Graduação em Patologia Molecular, Faculdade de Medicina, Universidade de Brasília, Brasília, DF, Brazil

Incorporating D-amino acid residues into antimicrobial peptides (AMPs) L- sequences,
generates diastereoisomers, improving resistance to proteolytic degradation and
favoring bioavailability. We studied the influence of D-arg and D-lys in three
computationally designed AMPs, PaDBS1R2, R6, and R7. Two groups were
synthesized, Group I (L-aa peptides) and Group II (all-D-arg and D-lys). Both groups
were evaluated for their susceptibility to degradation through serum stability assays.
Minimal inhibitory concentrations and minimal bactericidal concentration assays were
performed against ESKAPE strains. Circular dichroism (CD), nuclear magnetic
resonance (NMR), and computational studies were also conducted. Serum stability
assays revealed that group II, after 30 minutes of incubation, was 50% more resistant
to degradation than group I. By contrast, group II drastically compromised their
antibacterial effects due chirality inversion, whereas group I displayed a broad
spectrum of antibacterial activities from 3 to 32 μmol L-1. Cytotoxic/hemolytic properties
were not observed up to 100 μmol L-1 for all groups. CD and NMR studies revealed
group I adopted α-helix structures in 30% TFE and SDS. Group II displayed random
coil at those same conditions. Amide proton temperature coefficient analysis indicated
that group I preserved their secondary structure from 285-310 K. We concluded that
group II, although being resistant to proteolysis, does not adopt well-defined secondary
structures, abolishing its bioactivity. Further studies are proposed using computational
tools to predict punctual chirality modification, and a group containing D-arg and D-lys
residues outside the α-helical antibacterial pattern (KK[ILV]x(3)[AILV])) present in all
sequences here evaluated.

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