Polypeptides for treating and/or limiting influenza infection
Isolated polypeptides that recognize and are strong binders to Influenza A hemagglutinin and can be used, for example, to treat and/or limit development of an influenza infection, or to diagnose or monitor progression of an influenza infection are described.
1. An isolated polypeptide comprising an amino acid sequence according to general formula I
R1-R2-Phe-R3-R4-R5-R6-R7-R8-R9-R10-R11-R12-R13-R14-R15-R16 (SEQ ID NO: 1), wherein
R 1is selected from the group consisting of Ser, Ala, Phe, His, Lys, Met, Asn, Gln, Thr, Val, Tyr, and Asp;
R2 can be any amino acid;
R3 is selected from the group consisting of Asp, Ala, Glu, Gly, Asn, Pro, Ser, and
R4 is selected from the group consisting of Leu and Phe;
R5 can be any amino acid;
R6 is selected from the group consisting of Met, Phe, His, Ile, Leu, Gln, and Thr;
R7 is selected from the group consisting of Arg, Gly, Lys, Gln, and Thr;
R8 is selected from the group consisting of Ile, Asn, Gln, Val, and Trp;
R9 is selected from the group consisting of Met, Gly, Ile, Lys, Leu, Asn, Arg, Ser, Thr, Val, His, and Tyr;
R10 is selected from the group consisting of Trp and Phe;
R11 is selected from the group consisting of Ile, Phe, Ser, Thr, and Val;
R12 is selected from the group consisting of Tyr, Cys, Asp, Phe, His, Asn, and Ser;
R13 is selected from the group consisting of Val, Ala, Phe, fie, Leu, Asn, Gln, Thr, and Tyr;
R14 is selected from the group consisting of Phe, Glu, and Leu;
R15 is selected from the group consisting of Ala, Gly, Lys, Arg, and Ser; and
R16 is selected from the group consisting of Phe, Cys, His, Lys, Leu, Met, Asn, Gln, Arg, Thr, Val, Trp, and Tyr;
wherein the polypeptide is conjugated to a detectable tag.
2. The isolated polypeptide of claim 1 , wherein general formula I is
R1-R2-Phe-R3-R4-R5-R6-R7-R8-R9-R10-R11-R12-R13-R14-R15-R16-X1-R17(SEQ ID NO: 2), wherein
X1 is 4-8 amino acids in length, wherein each position can be any amino acid; and
R17 is Phe or Tyr.
3. The isolated polypeptide of claim 2 , wherein X1 comprises the amino acid sequence Z1-Arg-Z2-Ile-Pro (SEQ ID NO: 3), wherein Z1 is Lys or Asn, and Z2 is selected from the group consisting of Lys, Pro, and Thr.
4. The isolated polypeptide of claim 1 , wherein general formula I is A1-R1-R2-Phe-R3-R4-R5-R6-R7-R8-R9-R10-R11-R12-R13-R14-R15-R16-X1-R17-B1 (SEQ ID NO: 4), wherein at least one of A1 and B1 are present, and
wherein A1 comprises the amino acid sequence:
MSNAMDGQQLNRLLLEWIGAWDPFGLGKDAYD(D/V/Y)EA(A/D)(A/K/R)VL(Q/K)AVY(E/A)T(N/D) (SEQ ID NO: 5); and B1 comprises the amino acid sequence
(L/A/V)HA(Q/P)KLARRLLELK(Q/L)AASSPLP (SEQ ID NO: 6).
5. The isolated polypeptide of claim 4 , wherein both A1 and B1 are present.
6. The isolated polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence selected from the group consisting of SEQ ID NOS:7-11, 15-42, 44-53, and 55-82.
7. The isolated peptide of claim 1 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO:29.
8. The isolated polypeptide of claim 1 , wherein the detectable tag comprises colloidal gold.
9. A pharmaceutical composition, comprising one or more isolated polypeptides according to claim 1 and a pharmaceutically acceptable carrier.