| 主权项 |
1. A method of producing a compound comprising growing a host cell comprising a polynucleotide that encodes said compound in a suitable nutrient medium and isolating said compound from said cell or nutrient medium, wherein said compound binds to an mpl receptor and comprises the structure
TMP1-(L1)n-TMP2 wherein the C-terminus of the TMP1 peptide is linked to the N-terminus of the TMP2 peptide, optionally via L1,
wherein TMP1 and TMP2 are each independently selected from the group of core compounds comprising the structure selected from the group consisting of: a) X2-X3-X4-X5-X6-X7-X8-X9-X10,wherein,
X2 is selected from the group consisting of Glu, Lys, and Val;X3 is selected from the group consisting of Gly and Ala;X4 is Pro;X5 is selected from the group consisting of Thr and Ser;X6 is selected from the group consisting of Leu, Ile, Val, Ala, and Phe;X7 is selected from the group consisting of Arg and Lys;X8 is selected from the group consisting of Gln, Asn, and Glu;X9 is selected from the group consisting of Trp, Tyr, Cys, Ala, and Phe;X10 is selected from the group consisting of Leu, Ile, Val, Ala, Phe, Met, and Lys; b) X2-X3-X4-X5-X6-X7-X8-X9-X10, wherein,
X2 is selected from the group consisting of Glu, Asp, Lys, and Val;X3 is Ala;X4 is Pro;X5 is selected from the group consisting of Thr and Ser;X6 is selected from the group consisting of Leu, Ile, Val, Ala, and Phe;X7 is selected from the group consisting of Arg and Lys;X8 is selected from the group consisting of Gln, Asn, and Glu;X9 is selected from the group consisting of Trp, Tyr, Cys, Ala, and Phe;X10 is selected from the group consisting of Leu, Ile, Val, Ala, Phe, Met, and Lys; c) X2-X3-X4-X5-X6-X7-X8-X9-X10, wherein,
X2 is selected from the group consisting of Glu, Asp, Lys, and Val;X3 is selected from the group consisting of Gly and Ala;X4 is Pro;X5 is Ser;X6 is selected from the group consisting of Leu, Ile, Val, Ala, and Phe;X7 is selected from the group consisting of Arg and Lys;X8 is selected from the group consisting of Gln, Asn, and Glu;X9 is selected from the group consisting of Trp, Tyr, Cys, Ala, and Phe;X10 is selected from the group consisting of Leu, Ile, Val, Ala, Phe, Met, and Lys; d) X2-X3-X4-X5-X6-X7-X8-X9-X10, wherein,
X2 is selected from the group consisting of Glu, Asp, Lys, and Val;X3 is selected from the group consisting of Gly and Ala;X4 is Pro;X5 is selected from the group consisting of Thr and Ser;X6 is selected from the group consisting of Ile, Val, Ala, and Phe;X7 is selected from the group consisting of Arg and Lys;X8 is selected from the group consisting of Gln, Asn, and Glu;X9 is selected from the group consisting of Trp, Tyr, Cys, Ala, and Phe;X10 is selected from the group consisting of Leu, Ile, Val, Ala, Phe, Met, and Lys; e) X2-X3-X4-X5-X6-X7-X8-X9-X10, wherein,
X2 is selected from the group consisting of Glu, Asp, Lys, and Val;X3 is selected from the group consisting of Gly and Ala;X4 is Pro;X5 is selected from the group consisting of Thr and Ser;X6 is selected from the group consisting of Leu, Ile, Val, Ala, and Phe;X7 is Lys;X8 is selected from the group consisting of Gln, Asn, and Glu;X9 is selected from the group consisting of Trp, Tyr, Cys, Ala, and Phe;X10 is selected from the group consisting of Leu, Ile, Val, Ala, Phe, Met, and Lys; f) X2-X3-X4-X5-X6-X7-X8-X9-X10, wherein,
X2 is selected from the group consisting of Glu, Asp, Lys, and Val;X3 is selected from the group consisting of Gly and Ala;X4 is Pro;X5 is selected from the group consisting of Thr and Ser;X6 is selected from the group consisting of Leu, Ile, Val, Ala, and Phe;X7 is selected from the group consisting of Arg and Lys;X8 is selected from the group consisting of Gln and Asn;X9 is selected from the group consisting of Trp, Tyr, Cys, Ala, and Phe;X10 is selected from the group consisting of Leu, Ile, Val, Ala, Phe, Met, and Lys; g) X2-X3-X4-X5-X6-X7-X8-X9-X10, wherein,
X2 is selected from the group consisting of Glu, Asp, Lys, and Val;X3 is selected from the group consisting of Gly and Ala;X4 is Pro;X5 is selected from the group consisting of Thr and Ser;X6 is selected from the group consisting of Leu, Ile, Val, Ala, and Phe;X7 is selected from the group consisting of Arg and Lys;X8 is selected from the group consisting of Gln, Asn, and Glu;X9 is selected from the group consisting of Tyr, Cys, Ala, and Phe;X10 is selected from the group consisting of Leu, Ile, Val, Ala, Phe, Met, and Lys; and h) X2-X3-X4-X5-X6-X7-X8-X9-X10, wherein,
X2 is selected from the group consisting of Glu, Asp, Lys, and Val;X3 is selected from the group consisting of Gly and Ala;X4 is Pro;X5 is selected from the group consisting of Thr and Ser;X6 is selected from the group consisting of Leu, Ile, Val, Ala, and Phe;X7 is selected from the group consisting of Arg and Lys;X8 is selected from the group consisting of Gln, Asn, and Glu;X9 is selected from the group consisting of Trp, Tyr, Cys, Ala, and Phe;X10 is selected from the group consisting of Leu, Val, Ala, Phe, Met, and Lys; andwherein L1 is a linker; andn is 0 or 1, wherein when n is 1, L1 is independently selected from the linker groups consisting of Yn, wherein Y is a naturally occurring amino acid or a stereoisomer thereof and n is 1 through 20; and physiologically acceptable salts thereof. |
