Lactoferrampin, an antimicrobial peptide of bovine lactoferrin, exerts its candidacidal activity by a cluster of positively charged residues at the C-terminus in combination with a helix-facilitating N-terminal part.
The antimicrobial activity of bovine lactoferrin (bLF) is attributed to lactoferricin, which is situated in the N1-domain of bLF. Recently, another antimicrobial domain consisting of residues 268-284, designated lactoferrampin (LFampin), has been identified in the N1-domain of bLF, which exhibited antimicrobial activity against Candida albicans and several bacteria. In the present study, the candidacidal activity of a series of peptides spanning this antimicrobial domain was investigated in relation to the charge and the capacity to form a helical conformation in hydrophobic environments. C-Terminal truncation of LFampin resulted in a drastic decrease in candidacidal activity. Positively charged residues clustered at the C-terminal side of the LFampin domain appeared to be crucial for the candidacidal activity. The ability to adopt helical conformations did not change when LFampin was truncated at the C-terminal side. N-Terminally truncated LFampin peptides, truncated up to the sequence 270-284, were more reluctant to adopt a helical conformation. Therefore, we conclude that the C-terminal part of LFampin 265-284, which is the most active peptide, is crucial for its candidacidal activity, due to the presence of clustered positive charges, and that the N-terminal part is essential for activity as it facilitates helix formation.
van der Kraan
Marieke I A
MI
Department of Oral Biochemistry, Academic Center for Dentistry Amsterdam (ACTA), Vrije Universiteit, Van der Boechorststraat 7, NL-1081 BT Amsterdam, The Netherlands.
Nazmi
Kamran
K
Teeken
Afke
A
Groenink
Jasper
J
van 't Hof
Wim
W
Veerman
Enno C I
EC
Bolscher
Jan G M
JG
Nieuw Amerongen
Arie V
AV
D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects*; D002942:Circular Dichroism; D005434:Flow Cytometry; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007781:Lactoferrin; D007782:Lactoglobulins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017433:Protein Structure, Secondary
D000935:Antifungal Agents; D007782:Lactoglobulins; D010446:Peptide Fragments; C502040:lactoferrampin; D007781:Lactoferrin