title: Influence of Dimerization of Lipopeptide Laur-Orn-Orn-Cys-NH2and anN-terminal Peptide of Human Lactoferricin on Biological Activity.
abstract: Lactoferrin (LF) is a naturally occurring antimicrobial peptide that is cleaved by pepsin to lactoferricin (LFcin). LFcin has an enhanced antimicrobial activity as compared to that of LF. Recently several hetero- and homodimeric antimicrobial peptides stabilized by a single disulfide bond linking linear polypeptide chains have been discovered. We have demonstrated that the S-S bond heterodimerization of lipopeptide Laur-Orn-Orn-Cys-NH2(peptide III) and the syntheticN-terminal peptide of human lactoferricin (peptide I) yields a dimer (peptide V), which is almost as microbiologically active as the more active monomer and at the same time it is much less toxic. Furthermore, it has been found that the S-S bond homodimerization of both peptide I and peptide III did not affect antimicrobial and haemolytic activity of the compounds. The homo- and heterodimerization of peptides I and III resulted in either reduction or loss of antifungal activity. This work suggests that heterodimerization of antimicrobial lipopeptides via intermolecular disulfide bond might be a powerful modification deserving consideration in the design of antimicrobial peptides.
authors: Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308 Gdańsk, Poland.
authors: Elżbieta
authors: E
authors: Kamysz
authors: Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308 Gdańsk, Poland.
authors: Emilia
authors: E
authors: Sikorska
authors: Faculty of Pharmacy, Medical University of Gdańsk, Al. Gen. Hallera 107, 80-416 Gdańsk, Poland.
authors: Małgorzata
authors: M
authors: Dawgul
authors: Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308 Gdańsk, Poland.
authors: Rafał
authors: R
authors: Tyszkowski
authors: Faculty of Pharmacy, Medical University of Gdańsk, Al. Gen. Hallera 107, 80-416 Gdańsk, Poland.
authors: Wojciech
authors: W
authors: Kamysz
keywords: Antimicrobial activity; Circular dichroism; Haemolytic activity; Lactoferricin; Lactoferrin; Lipopeptide
references: Biochim Biophys Acta. 2001 Aug 15;1527(3):141-8
references: 11479030
references: Int J Pept Protein Res. 1983 Oct;22(4):464-8
references: 6654594
references: Antimicrob Agents Chemother. 2004 Dec;48(12):4919-21
references: 15561882
references: J Biol Chem. 2004 Mar 26;279(13):12277-85
references: 14709550
references: Antimicrob Agents Chemother. 1999 May;43(5):1267-9
references: 10223949
references: J Pept Sci. 2009 May;15(5):345-52
references: 19206074
references: Biopolymers. 1996;40(5):433-43
references: 9062067
references: J Appl Bacteriol. 1992 Dec;73(6):472-9
references: 1490908
references: J Antimicrob Chemother. 2003 May;51(5):1159-65
references: 12697647
references: J Antimicrob Chemother. 2011 Apr;66(4):859-62
references: 21393138
references: Biochemistry. 2005 Dec 13;44(49):16167-80
references: 16331977
references: Cell Mol Life Sci. 2005 Nov;62(22):2588-98
references: 16261252
references: Curr Pharm Des. 2003;9(16):1277-87
references: 12769736
references: J Biol Chem. 2004 Nov 19;279(47):48671-9
references: 15317821
references: Biochemistry. 2003 Jan 21;42(2):402-9
references: 12525167
references: Biochem J. 2005 Jan 1;385(Pt 1):135-43
references: 15344905
references: Arch Biochem Biophys. 1996 Apr 15;328(2):219-26
references: 8644997
references: Biochim Biophys Acta. 1999 Dec 15;1462(1-2):89-108
references: 10590304
references: Anal Biochem. 2000 Dec 15;287(2):252-60
references: 11112271
references: Antimicrob Agents Chemother. 2007 Jan;51(1):354-8
references: 17060532
references: Antimicrob Agents Chemother. 2003 Aug;47(8):2481-6
references: 12878508
references: Biochim Biophys Acta. 2006 Sep;1758(9):1426-35
references: 16616888
references: Antimicrob Agents Chemother. 2005 Aug;49(8):3387-95
references: 16048952
references: Future Med Chem. 2012 Aug;4(12):1541-51
references: 22917244
references: Biochem Cell Biol. 2002;80(1):65-74
references: 11908644
references: J Exp Med. 1969 Sep 1;130(3):643-58
references: 4979954
references: Biochem Biophys Res Commun. 2007 Nov 23;363(3):500-5
references: 17904104