Antimicrobial peptides and use thereof

Abstract

Antimicrobial agent including an artificially synthesized antimicrobial peptide that does not occur naturally is provided by present invention. The peptide included in the antimicrobial agent includes 1 unit, 2 units or more units of sequence(s) or sequence(s) with partial modification, the sequence(s) composed of at least 6 contiguous amino acid residues selected from any one of amino acid sequences: <tables id="TABLE-US-00001" num="1"> <table frame="none" colsep="0" rowsep="0" tabstyle="monospace"> <tgroup align="left" colsep="0" rowsep="0" cols="4"> <colspec colname="OFFSET" colwidth="56PT" align="left"/> <colspec colname="1" colwidth="70PT" align="left"/> <colspec colname="2" colwidth="91PT" align="left"/> <colspec colname="3" colwidth="0PT" align="left"/> <TBODY VALIGN="TOP"> <ROW> <ENTRY/> <ENTRY/> </ROW> <ROW> <ENTRY/> <ENTRY>(a)</ENTRY> <ENTRY>KVQIINKK;</ENTRY> <ENTRY/> </ROW> <ROW> <ENTRY/> <ENTRY> </ENTRY> </ROW> <ROW> <ENTRY/> <ENTRY>(b)</ENTRY> <ENTRY>SVQIVYKP;</ENTRY> </ROW> <ROW> <ENTRY/> <ENTRY> </ENTRY> </ROW> <ROW> <ENTRY/> <ENTRY>(c)</ENTRY> <ENTRY>QVEVKSEK;</ENTRY> </ROW> <ROW> <ENTRY/> <ENTRY> </ENTRY> </ROW> <ROW> <ENTRY/> <ENTRY>(d)</ENTRY> <ENTRY>KKVAVVRT;</ENTRY> </ROW> <ROW> <ENTRY/> <ENTRY> </ENTRY> </ROW> <ROW> <ENTRY/> <ENTRY>(e)</ENTRY> <ENTRY>KKVAIIRT;</ENTRY> </ROW> <ROW> <ENTRY/> <ENTRY> </ENTRY> </ROW> <ROW> <ENTRY/> <ENTRY>(f)</ENTRY> <ENTRY>KKPTSAK,</ENTRY> </ROW> <ROW> <ENTRY/> <ENTRY>and</ENTRY> </ROW> </TBODY> </TGROUP> </TABLE> </TABLES> the total number of amino acid residues included in 1 unit, 2 units or more units of sequence(s) is 30% or more of the total number of amino acid residues constituting the peptide chain.

1 . An antimicrobial agent comprising: 
 as a main component, an antimicrobial peptide having antimicrobial property against at least one kind of bacteria, said antimicrobial peptide including 1 unit, 2 units or more units of sequence(s) or said sequence(s) with partial modification, said sequence(s) composed of at least 6 contiguous amino acid residues selected from any one of the amino acid sequences:                                          (a)   KVQIINKK;                       (b)   SVQIVYKP;                   (c)   QVEVKSEK;                   (d)   KKVAVVRT;                   (e)   KKVAIIRT;                   (f)   KKPTSAK;         and                                        a carrier that can be pharmaceutically acceptable,    wherein a total number of amino acid residues included in said 1 unit, 2 units or more units of sequence(s) is 30% or more of a total number of amino acid residues constituting the peptide chain.    
     
     
         2 . The antimicrobial agent according to  claim 1 , wherein 2 or more units of said sequence(s) composed of at least 6 contiguous amino acid residues or said sequences with partial modification are arranged in proximity with each other.  
     
     
         3 . The antimicrobial agent according to  claim 1 , wherein said antimicrobial peptide further includes an amino acid sequence constituting nuclear localization signal sequence (NLS) or said amino acid sequence with partial modification and/or a sequence, or said sequence with partial modification, composed of at least 6 contiguous amino acid residues selected from an amino acid sequence constituting laminin binding site (LBS).  
     
     
         4 . The antimicrobial agent according to  claim 1 , wherein a total number of amino acid residues included in said antimicrobial peptide is 30 or less.  
     
     
         5 . The antimicrobial agent according to  claim 2 , wherein a total number of amino acid residues included in said antimicrobial peptide is 30 or less.  
     
     
         6 . The antimicrobial agent according to  claim 3 , wherein a total number of amino acid residues included in said antimicrobial peptide is 30 or less.  
     
     
         7 . The antimicrobial agent according to  claim 1 , wherein said antimicrobial peptide includes an amino acid sequence or said amino acid sequence with partial modification, said amino acid sequence is selected from the group consisting of SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35 and SEQ ID NO: 36, 
 wherein a total number of amino acid residues constituting the peptide chain of said antimicrobial peptide is 30 or less.    
     
     
         8 . An artificially synthesized antimicrobial peptide that does not occur naturally and having an antimicrobial property against at least one kind of bacteria, 
 wherein said antimicrobial peptide includes 2 or more units of sequences or said sequences with partial modification arranged in proximity with each other, said sequences composed of at least 6 contiguous amino acid residues selected from any one of the amino acid sequences:                                          (a)   KVQIINKK;                       (b)   SVQIVYKP;                   (c)   QVEVKSEK;                   (d)   KKVAVVRT;                   (e)   KKVAIIRT;                   (f)   KKPTSAK,         and                                        a total number of amino acid residues included in said 2 or more units of sequences is 30% or more of a total number of amino acid residues constituting the peptide chain.    
     
     
         9 . An artificially synthesized antimicrobial peptide that does not occur naturally and having an antimicrobial property against at least one kind of bacteria, 
 wherein said antimicrobial peptide includes 1 unit, 2 units or more units of sequence(s) or said sequence(s) with partial modification, said sequence(s) composed of at least 6 contiguous amino acid residues selected from any one of the amino acid sequences:                                          (a)   KVQIINKK                       (b)   SVQIVYKP;                   (c)   QVEVKSEK;                   (d)   KKVAVVRT;                   (e)   KKVAIIRT;                   (f)   KKPTSAK,                                       a total number of amino acid residues included in said 1 unit, 2 units or more units of sequence(s) is 30% or more of a total number of amino acid residues constituting the peptide chain, and    said antimicrobial peptide further includes an amino acid sequence constituting nuclear localization signal sequence (NLS) or said amino acid sequence with partial modification and/or a sequence, or said sequence with partial modification, composed of at least 6 contiguous amino acid residues selected from an amino acid sequence constituting laminin binding site (LBS).    
     
     
         10 . The antimicrobial peptide according to  claim 8 , wherein a total number of amino acid residues constituting the peptide chain of said antimicrobial peptide is 30 or less.  
     
     
         11 . The antimicrobial peptide according to  claim 9 , wherein a total number of amino acid residues constituting the peptide chain of said antimicrobial peptide is 30 or less.  
     
     
         12 . The antimicrobial peptide according to  claim 8 , wherein said antimicrobial peptide includes an amino acid sequence or said amino acid sequence with partial modification, said amino acid sequence is selected from the group consisting of SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35 and SEQ ID NO: 36.  
     
     
         13 . An artificially synthesized polynucleotide that does not occur naturally, said polynucleotide comprising a nucleotide sequence and/or a nucleotide sequence complementary to said nucleotide sequence, said nucleotide sequence encoding the antimicrobial peptide according to  claim 8 .  
     
     
         14 . A method for producing an antimicrobial peptide that does not occur naturally and has an antimicrobial property against at least one kind of bacteria, the method comprising: 
 (1) determining a sequence and/or said sequence with partial modification, said sequence composed of at least 6 contiguous amino acid residues selected from any one of the amino acid sequences:                                          (a)   KVQIINKK;                       (b)   SVQIVYKP;                   (c)   QVEVKSEK;                   (d)   KKVAVVRT;                   (e)   KKVAIIRT;                   (f)   KKPTSAK;                                       (2) arranging said determined sequence and/or said determined sequence with partial modification in 2 or more units in proximity with each other, and designing the peptide chain such that a total number of amino acid residues included in said 2 or more units of sequences is 30% or more of a total number of amino acid residues constituting the peptide chain; and    (3) synthesizing said designed peptide chain.    
     
     
         15 . A method for producing an antimicrobial peptide that does not occur naturally and has an antimicrobial property against at least one kind of bacteria, the method comprising: 
 (1) determining a sequence and/or said sequence with partial modification, said sequence composed of at least 6 contiguous amino acid residues selected from any one of the amino acid sequences:                                          (a)   KVQIINKK;                       (b)   SVQIVYKP;                   (c)   QVEVKSEK;                   (d)   KKVAVVRT;                   (e)   KKVAIIRT;                   (f)   KKPTSAK;                                       (2) designing the peptide chain such that said determined sequence and/or said determined sequence with partial modification include(s) 1 unit, 2 units or more units,    a total number of amino acid residues included in said 1 unit, 2 units or more units of amino acid sequences is 30% or more of a total number of amino acid residues, and    the peptide chain further includes an amino acid sequence constituting nuclear localization signal sequence (NLS) or said amino acid sequence with partial modification and/or a sequence, or said sequence with partial modification, composed of at least 6 contiguous amino acid residues selected from an amino acid sequence constituting laminin binding site (LBS); and    (3) synthesizing said designed peptide chain.    
     
     
         16 . The method according to  claim 14 , wherein the peptide chain is designed such that a total number of amino acid residues constituting the peptide chain is 30 or less.  
     
     
         17 . The method according to  claim 15 , wherein the peptide chain is designed such that a total number of amino acid residues constituting the peptide chain is 30 or less.