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Novel chemokine mimetics synthesis and their useRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), Peptide Containing (e.g., Protein, Peptones, Fibrinogen, Etc.) Doai, Cyclopeptides, 25 Or More Peptide Repeating Units In Known Peptide Chain StructureNovel chemokine mimetics synthesis and their use description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20070275892, Novel chemokine mimetics synthesis and their use. Brief Patent Description - Full Patent Description - Patent Application Claims
CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a divisional of prior U.S. application Ser. No. 10/222,703, filed Aug. 16, 2002, which is a continuation-in-part of prior U.S. application Ser. No. 10/086,177, filed Feb. 26, 2002, which is a continuation-in-part of U.S. application Ser. No. 09/835,107, filed Apr. 12, 2001, which claims the benefit of provisional U.S. Application No. 60/232,425, filed Apr. 12, 2001; U.S. application Ser. No. 10/086,177 claims the benefit of U.S. provisional Application Nos. 60/373,628, filed Apr. 17, 2002, and 60/373,629, filed Apr. 17, 2002; and each of these prior applications, specifically enumerated above, is hereby incorporated by reference in its entirety. FIELD OF THE INVENTION [0002] This invention relates to the preparation, design, derivation, and use of peptide agonists and antagonists of the chemokine SDF-1. In one aspect, this invention also relates to the preparation, design, or use of chemokine analogs for human SDF-1 or SDF-1/MIP-1.alpha. hybrids, or derivatives thereof. BACKGROUND OF THE INVENTION [0003] Chemokines (chemoattractant cytokines) are a family of homologous serum proteins of between 7 and 16 kDa, which were originally characterized by their ability to induce migration of leukocytes. Most chemokines have four characteristic cysteines (Cys), and depending on the motif displayed by the first two cysteines, they have been classified into CXC or alpha, CC or beta, C or gamma, and CX3C or delta chemokine classes. Two disulfide bonds are formed between the first and third cysteines and between the second and fourth cysteines. Clark-Lewis and co-workers reported that, at least for IL-8, the disulfide bridges are critical for chemokine activity (Clark-Lewis et al., J. Biol. Chem. 269:16075-16081, 1994). The only exception to the four cysteine motif is lymphotactin, which has only two cysteine residues. Thus, lymphotactin retains a functional structure with only one disulfide bond. [0004] In addition, the CXC, or alpha, subfamily has been divided into two groups depending on the presence of the ELR motif (Glu-Leu-Arg) preceding the first cysteine: the ELR-CXC chemokines and the non-ELR-CXC chemokines (see, e.g. Clark-Lewis, supra, and Belperio et al., "CXC Chemokines in Angiogenesis," J. Leukoc. Biol. 68:1-8, 2000). [0005] ELR-CXC chemokines, such as IL-8, are generally strong neutrophil chemoattractants while non-ELR chemokines, such as IP-10, and SDF-1, predominantly recruit lymphocytes. CC chemokines, such as RANTES, MIP-1-alpha, MCP-1, generally function as chemoattractants for monocytes, basophils, eosinophils, and T-cells but not neutrophils. In general, chemokines are chemotactic agents that recruit leukocytes to the sites of injuries. SDF-1 [0006] Stromal cell-derived factor-1 (SDF-1 or CXCL12) is a CXC chemokine that demonstrates in vitro activity with respect to lymphocytes and monocytes but not neutrophils. It is a highly potent in vivo chemoattractant for mononuclear cells. SDF-1 has been shown to induce intracellular actin polymerization in lymphocytes, and to induce a transient elevation of cytoplasmic calcium in some cells. MIP-1.alpha. [0007] Macrophage inflammatory protein-1.alpha. (MIP-1.alpha., MIP-1-alpha or CCL3) is a factor produced by macrophages in response to their stimulation by bacterial endotoxins. It activates neutrophils, eosinophils, and basophils and appears to play a role in inflammation. Additionally, it is especially potent as a basophil agonist, and appears to act through a rapid rise in intracellular calcium, and causes the release of histamine, sulfido-leukotrienes, and also plays a role in chemotaxis. MIP-1-alpha may also act to inhibit stem cell proliferation. Chemokine Receptors [0008] The receptors for chemokines are G-protein coupled seven-transmembrane receptors. Based on the chemokine class they bind, the receptors have been named CXCR1, CXCR2, CXCR3, CXCR4, and CXCR5 (all of which bind CXC chemokines); CCR1 through CCR9 (all of which bind CC chemokines); XCR1 (which binds the C chemokine, Lptn); and CX3CR1 (which binds the CX3C chemokine, fractalkine or neurotactin). (See Table 1.) [0009] The chemokines and their receptors have received increasing attention in the last few years. In addition to their role in HIV pathogenesis, it is now clear that chemokines participate in many pathological conditions such as inflammation and diseases or conditions associated with autoimmune responses. They also play a very important role in normal homeostasis, including lymphoid development and migration. Further, they play a role in the growth of bones. As a result of their role in various physiological processes and pathological conditions and diseases, chemokines have many important potential therapeutic applications. TABLE-US-00001 TABLE 1 Chemokine receptors Human chemokine ligands CXCR1 IL-8, GCP-2 CXCR2 IL-8, GCP-2, Gro .alpha., Gro .beta., Gro .gamma., ENA-78, PBP CXCR3 MIG, IP-10, I-TAC CXCR4 SDF-1/PBSF CCR1 MIP-1 .alpha., MIP-1 .beta., RANTES, HCC-1, 2, 3, and 4 CCR2 MCP-1, MCP-2, MCP-3, MCP-4 CCR3 Eotaxin-1 eotaxin-2, MCP-3 CCR4 TARC, MDC, MIP-1 .alpha., RANTES CCR5 MIP-1 .alpha., MIP-1 .beta., RANTES CCR6 MIP-3 .alpha./LARC CCR7 MIP-3 .beta./ELC, 6Ckine/LC CCR8 I-309 CCR9 TECK CCR10 CCL27, CCL28(hMEC) [0010] Certain agonists of CXCR4 have been described in International Publication No. WO 01/76615 A2 entitled "CXCR4 Agonist Treatment of Hematopoietic Cells" (PCT/CA01/00540). Certain antagonists of CXCR4 have been described in International Publication No. WO 01/85196 A2 entitled "CXCR4 Antagonist Treatment of Hematopoietic Cells" (PCT/CA01/00659. Both PCT publications are hereby incorporated by reference herein, including any drawings, figures and tables. SUMMARY OF THE INVENTION [0011] The embodiments of the present invention generally encompass compositions comprising SDF-1 mimetics and methods of using them to modulate an activity of a cell having an SDF-1 receptor. In some embodiments, the methods comprise binding the SDF-1 receptor of the cell with an SDF-1 mimetic consisting of the following structure: TABLE-US-00002 R.sub.N-HN-Xaa.sub.3-Pro-Val-Ser-Leu-Ser- (SEQ ID NO: 10). Tyr-Arg-Xaa.sub.1-Pro-Xaa.sub.2-Arg-Phe- Phe-[linker]-Leu-Lys-Trp-Ile- Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu- Asn-R.sub.C [0012] R.sub.N can be an N-terminal modifier that comprises a component selected from a group consisting of hydrogen, poly(ethylene glycol), a biochemical label, a radiolabel, an acyl group, an acetyl group, and an N-terminal modifier capable of reducing the ability of the SDF-1 mimetic to act as a substrate for aminopeptidases. R.sub.C can be a C-terminal modifier that comprises a component selected from a group consisting of a hydroxyl group, poly(ethylene glycol), a biochemical label, a radiolabel, an amido group, and a C-terminal modifier capable of reducing the ability of the SDF-1 mimetic to act as a substrate for carboxypeptidases. The Xaa.sub.1, Xaa.sub.2, and Xaa.sub.3 variables can be each independently selected from a group consisting of (a) any natural amino acid; and (b) any non-natural amino acid having the structure H.sub.2N-Z.sub.A-COOH, where Z.sub.A is selected from a group consisting of saturated and unsaturated aliphatics and heteroaliphatics consisting of 20 or fewer carbon atoms, cycloalkyl amines, and fused cycloalkyl amines. The linker can be selected from a group consisting of (a) any combination of four natural amino acids; and (b) any non-natural amino acid having the structure H.sub.2N-Z.sub.A-COOH, wherein Z.sub.A is selected from a group consisting of saturated and unsaturated aliphatics and heteroaliphatics consisting of 20 or fewer carbon atoms that are optionally substituted with a hydroxyl, carboxyl, carbonyl, thiol, amino, amido, imino, or an aromatic group having from 5 to 7 members in the ring; and --(CH.sub.2).sub.n--, wherein n is an integer ranging from 9 to 14. [0013] The cell can be a hematopoietic cell selected from a group consisting of hematopoietic stem cells, hematopoietic progenitor cells, primitive granulocytes, primitive erythroid cells, leukocytes, and neutrophils. In some embodiments, the binding can reduce the rate of multiplication of the cell or, where the cell is a quiescent cell, the binding can repress the activation of the quiescent cell. [0014] In some embodiments, the invention is a method of modulating an activity of hematopoietic cells in a subject comprising administering an effective amount of a composition comprising the SDF-1 mimetic to the subject. In these embodiments, the administering can result in mobilizing the hematopoietic cells; and enhancing recovery of the hematopoietic cells following chemotherapy, such as by reducing the rate of multiplication of the hematopoietic cells to inhibit the effect of a cytotoxic agent on the hematopoietic cells during the chemotherapy. In some embodiments, the administering can result in enhancing an engraftment of the hematopoietic cells from the subject in a second subject. In some embodiments, the method further comprises administering a second agent, wherein the administering of the second agent is sequential or concurrent to the administering of the composition comprising the SDF-1 mimetic. In these embodiments, the second agent can include G-CSF. [0015] In some embodiments, the invention includes method of increasing the number of hematopoietic cells circulating in the blood of a subject, wherein the method comprises administering an effective amount of a composition comprising an SDF-1 mimetic. BRIEF DESCRIPTION OF THE DRAWINGS [0016] FIG. 1 shows the induction of [Ca.sup.2+].sub.i mobilization by SDF-1 and SDF-1 analogs. Fluo-4,AM loaded SUP-T1 cells (5.times.10.sup.6/ml) were stimulated with SDF-1, Compound A (SEQ ID NO:809), Compound B (SEQ ID NO:810), Compound C (SEQ ID NO:811), Compound D (SEQ ID NO:812) and Compound E (SEQ ID NO:813) at the concentrations indicated. The values represent the mean+/-one S.D. of one representative experiment from three independent experiments. Continue reading about Novel chemokine mimetics synthesis and their use... Full patent description for Novel chemokine mimetics synthesis and their use Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Novel chemokine mimetics synthesis and their use patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. 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