Selective acylation enhances membrane charge sensitivity of the antimicrobial peptide mastoparan-x.
The partitioning of the wasp venom peptide mastoparan-X (MPX) into neutral and negatively charged lipid membranes has been compared with two new synthetic analogs of MPX where the N(α)-terminal of MPX was acylated with propanoic acid (PA) and octanoic acid (OA). The acylation caused a considerable change in the membrane partitioning properties of MPX and it was found that the shorter acylation with PA gave improved affinity and selectivity toward negatively charged membranes, whereas OA decreased the selectivity. Based on these findings, we hypothesize that minor differences in the embedding and positioning of the peptide in the membrane caused by either PA or OA acylation play a critical role in the fine-tuning of the effective charge of the peptide and thereby the fine-tuning of the peptide's selectivity between neutral and negatively charged lipid membranes. This finding is unique compared to previous reports where peptide acylation enhanced membrane affinity but also resulted in impaired selectivity. Our result may provide a method of enhancing selectivity of antimicrobial peptides toward bacterial membranes due to their high negative charge-a finding that should be investigated for other, more potent antimicrobial peptides in future studies.
Department of Micro- and Nanotechnology, DTU Nanotech, Technical University of Denmark, Lyngby, Denmark.
Thomas
T
Etzerodt
Jonas R
JR
Henriksen
Palle
P
Rasmussen
Mads H
MH
Clausen
Thomas L
TL
Andresen
D000215:Acylation / Q000502:physiology*; D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000378:metabolism; D002210:Caprylates / Q000737:chemistry*; D002942:Circular Dichroism; D005452:Fluoresceins; D006461:Hemolysis / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D008051:Lipid Bilayers / Q000737:chemistry; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D014862:Wasp Venoms / Q000737:chemistry
D023181:Antimicrobial Cationic Peptides; D002210:Caprylates; D005452:Fluoresceins; D036341:Intercellular Signaling Peptides and Proteins; D008051:Lipid Bilayers; D010455:Peptides; D014862:Wasp Venoms; C071123:mastoparan X
FEBS Lett. 1997 Feb 17;403(2):208-12
9042968
Biochem J. 2005 Jan 1;385(Pt 1):135-43
15344905
Biochim Biophys Acta. 2000 Nov 23;1508(1-2):69-85
11090819
Biopolymers. 2000;55(1):4-30
10931439
Biochim Biophys Acta. 1998 Nov 10;1376(3):391-400
9804997
J Biol Chem. 2004 Mar 26;279(13):12277-85
14709550
Antimicrob Agents Chemother. 2006 Dec;50(12):4153-60
17043126
Biochem J. 2005 Sep 15;390(Pt 3):695-702
15907192
Biochemistry. 1995 Mar 14;34(10):3423-9
7533538
Anal Biochem. 2000 Oct 15;285(2):235-45
11017708
Int J Antimicrob Agents. 2003 Jan;21(1):13-9
12507833
Biophys J. 2006 Aug 15;91(4):1368-79
16714348
Biopolymers. 1986;25 Suppl:S115-21
3779021
Annu Rev Biophys Biophys Chem. 1989;18:113-36
2660821
Antimicrob Agents Chemother. 1998 Sep;42(9):2206-14
9736536
J Antimicrob Chemother. 2003 May;51(5):1159-65
12697647
Biochim Biophys Acta. 1998 Mar 2;1369(2):267-77
9518645
Biochemistry. 2002 Feb 19;41(7):2254-63
11841217
Eur J Biochem. 2001 Nov;268(21):5589-600
11683882
J Struct Biol. 2008 Apr;162(1):121-38
18180166
J Colloid Interface Sci. 2010 May 15;345(2):160-7
20185142
Bioconjug Chem. 2004 May-Jun;15(3):530-5
15149180
Biophys Chem. 2002 May 2;96(2-3):191-201
12034440
Biophys J. 1991 Aug;60(2):341-51
1912277
Biochemistry. 1997 May 20;36(20):6124-32
9166783
Chem Biol Drug Des. 2010 Jun;75(6):563-9
20374251
Biochim Biophys Acta. 2004 Nov 3;1666(1-2):40-50
15519307
FEBS Lett. 2001 Jul 20;501(2-3):146-50
11470274
Proteins. 1995 Jun;22(2):182-6
7567965
Biophys J. 1978 Jan;21(1):35-70
620077
Biochem Biophys Res Commun. 2004 Feb 6;314(2):615-21
14733952
Trends Microbiol. 1997 Jan;5(1):37-42
9025234
Antimicrob Agents Chemother. 2005 Jun;49(6):2412-20
15917541
Biochim Biophys Acta. 1998 Nov 10;1376(3):339-52
9804985
J Mol Biol. 2001 Jun 8;309(3):543-52
11397078
Nat Rev Microbiol. 2005 Mar;3(3):238-50
15703760
Biochemistry. 2010 May 18;49(19):4076-84
20387900
Biochemistry. 1990 Dec 11;29(49):10995-1000
2271694
Biochem J. 2004 Feb 15;378(Pt 1):93-103
14609430
Biochem Pharmacol. 1999 Jan 15;57(2):121-34
9890560
Biopolymers. 2008;90(3):369-83
18098173
J Biol Chem. 1983 Nov 25;258(22):13697-702
6643447