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US 6,333,395 B1Granted
Compositions for inhibition of membrane fusion-associated events, including human parainfluenza virus transmission
OwnerShawn Barney, Dennis Lambert +1inventors
InventorsShawn Barney, Dennis Lambert, Stephen Robert Petteway
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Abstract
The present invention relates to peptides which exhibit potent anti-retroviral activity. The peptides of the invention comprise DP178 (SEQ ID NO:1) peptide corresponding to amino acids 638 to 673 of the HIV-1LAI gp41 protein, and fragments, analogs and homologs of DP178. The invention further relates to the uses of such peptides as inhibitory of human and non-human retroviral, especially HIV, transmission to uninfected cells.
Claims107
An isolated peptide consisting of:
- (a) an amino acid sequence of a 16 to 39 amino acid residue region of a human parainfluenza virus protein, wherein said region is identified by:
- (i) 4 or 5 heptad repeats of an ALLMOTI5 sequence search motif;
- (ii) 4 or 5 heptad repeats of a 107×178×4 sequence search motif;
- or
- (iii) a PLZIP sequence search motif, and
- (b) an amino terminal X, and a carboxy terminal Z in which:
- X comprises an amino group, an acetyl group, a 9-fluorenylmethoxy-carbonyl group, a hydrophobic group, a macromolecular carrier group;
- and
- Z comprises a carboxyl group, an amido group, a hydrophobic group, or a macromolecular carrier group.
6 more elements
An isolated peptide having the formula:
- X-TLNNSVALDPIDISIELNKAKSDLEESKEWIRRSN-Z (SEQ ID NO:33);
- X-LNNSVALDPIDISIELNKAKSDLEESKEWIRRSNQ-Z (SEQ ID NO:34);
- X-NNSVALDPIDISIELNKAKSDLEESKEWIRRSNQK-Z (SEQ ID NO:35);
- X-NSVALDPIDISIELNKAKSDLEESKEWIRRSNQKL-Z (SEQ ID NO:36);
- X-SVALDPIDISIELNKAKSDLEESKEWIRRSNQKLD-Z (SEQ ID NO:37);
- X-VALDPIDISIELNKAKSDLEESKEWIRRSNQKLDS-Z (SEQ ID NO:38);
- X-ALDPIDISIELNKAKSDLEESKEWIRRSNQKLDSI-Z (SEQ ID NO:39);
- X-LDPIDISIELNKAKSDLEESKEWIRRSNQKLDSIG-Z (SEQ ID NO:40);
- X-DPIDISIELNKAKSDLEESKEWIRRSNQKLDSIGN-Z (SEQ ID NO:41);
- X-PIDISIELNKAKSDLEESKEWIRRSNQKLDSIGNW-Z (SEQ ID NO:42);
- X-IDISIELNKAKSDLEESKEWIRRSNQKLDSIGNWH-Z (SEQ ID NO:43);
- X-DISIELNKAKSDLEESKEWIRRSNQKLDSIGNWHQ-Z (SEQ ID NO:44);
- X-ISIELNKAKSDLEESKEWIRRSNQKLDSIGNWHQS-Z (SEQ ID NO:45);
- X-SIELNKAKSDLEESKEWIRRSNQKLDSIGNWHQSS-Z (SEQ ID NO:46);
- X-IELNKAKSDLEESKEWIRRSNQKLDSIGNWHQSST-Z (SEQ ID NO:47);
- X-ELNKAKSDLEESKEWIRRSNQKLDSIGNWHQSSTT-Z (SEQ ID NO:48);
- X-TAAVALVEAKQARSDIEKLKEAIRDTNKAVQSVQS-Z (SEQ ID NO:49);
- X-AVALVEAKQARSDIEKLKEAIRDTNKAVQSVQSSI-Z (SEQ ID NO:50);
- X-LVEAKQARSDIEKLKEAIRDTNKAVQSVQSSIGNL-Z (SEQ ID NO:51);
- X-VEAKQARSDIEKLKEAIRDTNKAVQSVQSSIGNLI-Z (SEQ ID NO:52);
- X-EAKQARSDIEKLKEAIRDTNKAVQSVQSSIGNLIV-Z (SEQ ID NO:53);
- X-AKQARSDIEKLKEAIRDTNKAVQSVQSSIGNLIVA-Z (SEQ ID NO:54);
- X-KQARSDIEKLKEAIRDTNKAVQSVQSSIGNLIVAI-Z (SEQ ID NO:55);
- X-QARSDIEKLKEAIRDTNKAVQSVQSSIGNLIVAIK-Z (SEQ ID NO:56);
- X-ARSDIEKLKEAIRDTNKAVQSVQSSIGNLIVAIKS-Z (SEQ ID NO:57);
- X-RSDIEKLKEAIRDTNKAVQSVQSSIGNLIVAIKSV-Z (SEQ ID NO:58);
- X-SDIEKLKEAIRDTNKAVQSVQSSIGNLIVAIKSVQ-Z (SEQ ID NO:59);
- X-KLKEAIRDTNKAVQSVQSSIGNLIVAIKSVQDYVN-Z (SEQ ID NO:60);
- X-LKEAIRDTNKAVQSVQSSIGNLIVAIKSVQDYVNK-Z (SEQ ID NO:61);
- or
- X-AIRDTNKAVQSVQSSIGNLIVAIKSVQDYVNKEIV-Z (SEQ ID NO:62)
- in which:
- amino acid residues are presented by the single-letter code;
- X comprises an amino group, an acetyl group, a 9-fluorenylmethoxy-carbonyl group, a hydrophobic group, or a macromolecular carrier group;
- Z comprises a carboxyl group, an amido group, a hydrophobic group, or a macromolecular carrier group.
32 more elements
An isolated peptide consisting of:
- (a) an amino acid sequence of a 16 to 39 amino acid residue region of a human parainfluenza virus protein, wherein said region is identified by:
- (i) 4 or 5 heptad repeats of an ALLMOTI5 sequence search motif,
- (ii) 4 or 5 heptad repeats of a 107×78×4 sequence search motif, or
- (iii) a PLZIP sequence search motif;
- (b) an amino terminal insertion of about 2 to about 50 human parainfluenza virus protein amino acid residues amino to the region of the human parainfluenza virus protein identified by the sequence search motif;
- and
- (c) an amino terminal X and a carboxy terminal Z, in which
- X comprises an amino group, an acetyl group, a 9-fluorenylmethoxy-carbonyl group, a hydrophobic group, or a macromolecular carrier group, and
- Z comprises a carboxyl group, an amido group, a hydrophobic group, or a macromolecular carrier group.
6 more elements
An isolated peptide consisting of:
- (a) an amino acid sequence of a 16 to 39 amino acid residue region of a human parainfluenza virus protein, wherein said region is identified by:
- (i) 4 or 5 heptad repeats of an ALLMOTI5 sequence search motif,
- (ii) 4 or 5 heptad repeats of a 107×178×4 sequence search motif, or
- (iii) a PLZIP sequence search motif;
- (b) an carboxy terminal insertion of about 2 to about 50 human parainfluenza virus protein amino acid residues carboxy to the region of the human parainfluenza virus protein identified by the sequence search motif;
- and
- (c) an amino terminal X and a carboxy terminal Z, in which
- X comprises an amino group, an acetyl group, a 9-fluorenylmethoxy-carbonyl group, a hydrophobic group, or a macromolecular carrier group, and
- Z comprises a carboxyl group, an amido group, a hydrophobic group, or a macromolecular carrier group.
6 more elements
An isolated peptide consisting of:
- (a) an amino acid sequence of a 16 to 39 amino acid residue region of a human parainfluenza virus protein, wherein said region is identified by:
- (i) 4 or 5 heptad repeats of an ALLMOTI5 sequence search motif,
- (ii) 4 or 5 heptad repeats of a 107×178×4 sequence search motif, or
- (iii) a PLZIP sequence search motif;
- (b) an amino terminal insertion of about 2 to about 50 human parainfluenza virus protein amino acid residues amino to the region of the human parainfluenza virus protein identified by the sequence search motif;
- (c) an carboxy terminal insertion of about 2 to about 50 human parainfluenza virus protein amino acid residues carboxy to the region of the human parainfluenza virus protein identified by the sequence search motif, and
- (d) an amino terminal X and a carboxy terminal Z, in which
- X comprises an amino group, an acetyl group, a 9-fluorenylmethoxy-carbonyl group, a hydrophobic group, or a macromolecular carrier group, and
- Z comprises a carboxyl group, an amido group, a hydrophobic group, or a macromolecular carrier group.
6 more elements
Dependencies are inferred from the claim text.