Review
Tryptophan- and arginine-rich antimicrobial peptides: Structures and mechanisms of action

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Abstract

Antimicrobial peptides encompass a number of different classes, including those that are rich in a particular amino acid. An important subset are peptides rich in Arg and Trp residues, such as indolicidin and tritrpticin, that have broad and potent antimicrobial activity. The importance of these two amino acids for antimicrobial activity was highlighted through the screening of a complete combinatorial library of hexapeptides. These residues possess some crucial chemical properties that make them suitable components of antimicrobial peptides. Trp has a distinct preference for the interfacial region of lipid bilayers, while Arg residues endow the peptides with cationic charges and hydrogen bonding properties necessary for interaction with the abundant anionic components of bacterial membranes. In combination, these two residues are capable of participating in cation–π interactions, thereby facilitating enhanced peptide–membrane interactions. Trp sidechains are also implicated in peptide and protein folding in aqueous solution, where they contribute by maintaining native and nonnative hydrophobic contacts. This has been observed for the antimicrobial peptide from human lactoferrin, possibly restraining the peptide structure in a suitable conformation to interact with the bacterial membrane. These unique properties make the Arg- and Trp-rich antimicrobial peptides highly active even at very short peptide lengths. Moreover, they lead to structures for membrane-mimetic bound peptides that go far beyond regular α-helices and β-sheet structures. In this review, the structures of a number of different Trp- and Arg-rich antimicrobial peptides are examined and some of the major mechanistic studies are presented.

Abbreviations

BLM
black lipid membranes
CD
circular dichroism
cLZ
human c-type lysozyme
combi-1 (or-2)
combinatorial peptide-1 (or-2)
CPP
cell-permeable peptide
DiPoPE
dipalmitoleoyl PE
DOPC (or DOPE or DOPG)
1,2-dioleoyl-sn-glycero-3-PC (or PE, PG)
DPC
dodecylphosphocholine
DPPC (or DPPE or DPPG)
1,2-dipalmitoyl-sn-glycero-3-PC (or PE or PG)
DSC
differential scanning calorimetry
HEWL
hen egg white lysozyme
hLZ
human lysozyme
IC50
inhibitory concentration at which 50% inhibition is achieved
ITC
isothermal titration calorimetry
Lfcin
lactoferricin
LfcinB
bovine Lfcin
LPS
lipopolysaccharide
LUV
large unilamellar vesicle
LysC
HEWL peptide, residues 98–112 in HEWL
LysH
residues 107–113 in hLZ
MD
molecular dynamics
MIC
minimal inhibitory concentration
MIP-3α
macrophage inflammatory protein-3α
MRSA
methicillin resistant Staphylococcus aureus
NMR
nuclear magnetic resonance
NOE
nuclear Overhauser effect
PC
phosphatidylcholine
PE
phosphatidylethanolamine
PG
phosphatidylglycerol
PDB
Protein Data Bank
PIN-a (or-b)
puroindoline A (or B)
puroA (or B)
puroindoline A (or B) peptide
SDS
sodium dodecyl sulfate
SMH
Shai–Matsuzaki–Huang
VRE
vancomycin resistant enterococci

Keywords

Antimicrobial peptide
Structure
Tryptophan
Arginine
Cation–π interaction

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