US 2005/0272645 A1 - Retrocyclins: Antiviral And Antimicrobial Peptides - The Lens - Free & Open Patent and Scholarly Search

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US 2005/0272645 A1

Retrocyclins: Antiviral And Antimicrobial Peptides

Published: Dec 8, 2005
Family: 5
Cited Works: 0
Cited by: 7
Cites: 9
Sequences: 135
Additional Info: Full text Published Sequence

Abstract

Retrocyclin peptides are small antimicrobial agents with potent activity against bacteria and viruses. The peptides are nonhemolytic, and exhibit minimal in vitro cytotoxicity. A pharmaceutical composition comprising retrocyclin as an active agent is administered therapeutically to a patient suffering from a bacterial and/or viral infection, or to an individual facing exposure to a bacterial and/or viral infection, especially one caused by the HIV-1 retrovirus or other sexually-transmitted pathogens.

Claims

An isolated retrocyclin peptide.
The isolated retrocyclin peptide according to claim 1, wherein said peptide is encoded by one or more primate genetic sequences.
The isolated retrocyclin peptide according to claim 2, wherein said peptide is encoded by one or more human genetic sequences.
The isolated retrocyclin peptide according to claim 1, wherein said peptide is linear.
The isolated retrocyclin peptide according to claim 1, wherein said peptide is circular.
The isolated retrocyclin according to claim 1, wherein said peptide is two linked nonapeptides, wherein each nonapeptide sequence is independently selected from the group consisting of SEQ ID NO:19 to SEQ ID NO:64; and SEQ ID NO:74 to SEQ ID NO:119.
The isolated retrocyclin according to claim 1, wherein said peptide is two linked nonapeptides, wherein each nonapeptide sequence is independently selected from the group consisting of SEQ ID NO:25 and SEQ ID NO:33.
The isolated retrocyclin according to claim 1, wherein said peptide is two linked nonapeptides, wherein each nonapeptide sequence is independently selected from the group consisting of a sequence within the formula: R ^R/_KI C G ^R/_K^R/K/_GI CX₁X₂ X₃X₄X₅X₆ X₇ X₈X₉
The isolated peptide according to claim 6, wherein at least one of said nonamers comprises an arginine to lysine or lysine analog substitution at residue 6.
A cyclic polypeptide comprising the amino acid sequence: X₁X₂X₃X₄X₅X₆X₇X₈X₉X₁₀X₁₁X₁₂X₁₃X₁₄X₁₅X₁₆X₁₇X₁₈
wherein X1 and X18 are linked through a peptide bond,

disulfide crosslinks are formed between at least one of: X₃and X₁₆; X₅and X₁₄, and X₇and X₁₂with the proviso that when such a crosslink is present, the crosslinked amino acids are both cysteines;

at least about three of amino acids X₁to X₁₈are arginine or lysine;

X₂, X₅, X₁₁, X₁₅are aliphatic amino acids; and

X₁, X₁₀and X₁₇are glycine or alanine.
The cyclic polypeptide according to claim 10, wherein three pairs of cysteines are crosslinked.
The cyclic polypeptide of claim 10, wherein said polypeptide comprises the amino acid sequence set forth in SEQ ID NO:1-10.
The cyclic polypeptide of claim 10, wherein said polypeptide comprises the amino acid sequence set forth in SEQ ID NO:1, 2, 5 or 8.
The cyclic polypeptide of claim 1, and a pharmaceutically acceptable excipient.
An isolated nucleic acid encoding a primate retrocyclin or a peptide set forth in SEQ ID NO:1-10.
An isolated nucleic acid according to claim 15, wherein said retrocyclin is human.
The isolated nucleic acid according to claim 16, wherein said nucleic acid comprises the sequence set forth in SEQ ID NO:11, SEQ ID NO:119, SEQ ID NO:121, or SEQ ID NO:123.
A method for preventing retroviral infection in a cell, the method comprising:
administering an effective dose of a circular minidefensin or retrocyclin to said cell.
The method according to claim 18, wherein said cell is of a type that is susceptible to bacterial or viral infection.
A method for killing microbial organisms, the method comprising:
administering an effective dose of retrocyclin to said microbial organisms.
A method for administering retrocyclin as a therapeutic agent to a patient with an established microbial or viral infection.
A method for administering retrocyclin as a prophylactic agent to prevent a microbial or viral infection in a patient at risk of developing such infection.

Owners (US)

The Regents Of The University Of California (Jun 28 2005)
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Applicants

Univ California
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Inventors

Lehrer Robert I
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Waring Alan J
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Cole Alexander M
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Hong Teresa B
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CPC Classifications

A61K38/00
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C07K7/06
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C07K7/08
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C07K7/64
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IPC Classifications

A61K38/00
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C07K7/64
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US Classifications

514/9.000
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530/317.000
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536/23.500
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Document History

Publication: Dec 8, 2005
US 2005/0272645 A1
Application: Nov 5, 2004
US 98214504 A
Priority: Nov 5, 2004
US 98214504 A
Priority: May 6, 2003
US 0314106 W
Priority: May 6, 2002
US 14164502 A
Priority: Apr 18, 2002
US 0212353 W
Priority: Apr 18, 2001
US 28485501 P