Bactericidal activity of LFchimera is stronger and less sensitive to ionic strength than its constituent lactoferricin and lactoferrampin peptides.
The innate immunity factor lactoferrin harbours two antimicrobial moieties, lactoferricin and lactoferrampin, situated in close proximity in the N1 domain of the molecule. Most likely they cooperate in many of the beneficial activities of lactoferrin. To investigate whether chimerization of both peptides forms a functional unit we designed a chimerical structure containing lactoferricin amino acids 17-30 and lactoferrampin amino acids 265-284. The bactericidal activity of this LFchimera was found to be drastically stronger than that of the constituent peptides, as was demonstrated by the need for lower dose, shorter incubation time and less ionic strength dependency. Likewise, strongly enhanced interaction with negatively charged model membranes was found for the LFchimera relative to the constituent peptides. Thus, chimerization of the two antimicrobial peptides resembling their structural orientation in the native molecule strikingly improves their biological activity.
Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Van der Boechorststraat 7, NL-1081BT, Amsterdam, The Netherlands. jgm.bolscher@vumc.nl
Jan G M
JG
Bolscher
Regina
R
Adão
Kamran
K
Nazmi
Petra A M
PA
van den Keybus
Wim
W
van 't Hof
Arie V
AV
Nieuw Amerongen
Margarida
M
Bastos
Enno C I
EC
Veerman
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002152:Calorimetry, Differential Scanning; D002942:Circular Dichroism; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D007781:Lactoferrin / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D007782:Lactoglobulins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009994:Osmolar Concentration; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D007782:Lactoglobulins; D010446:Peptide Fragments; D010455:Peptides; D011993:Recombinant Fusion Proteins; C502040:lactoferrampin; C082171:lactoferricin B; D007781:Lactoferrin