Claims
- 1. A method for screening a candidate substance for binding to and/or inhibiting binding to CEACAM1 or a structurally related CEA family member of a ligand or inhibiting a biological activity such as cell adhesion, tumor metastasis, angiogenesis, virus binding and infection, or (bacterial inhibiting, or cell adhesion inhibiting) activity comprising:
preparing a soluble CEACAM1 protein comprising a functional binding domain, D1, having a protruding, convoluted CC′ loop amino acid sequence for humans of K G E R V D G N R Q); a C-TERMINAL domain, D4, having an elongated CD loop, and a flexible linker connecting D1 to D4, to provide a target protein; preparing a control sample comprising the target protein and a monoclonal antibody having specific binding affinity for the CC′ loop, and preparing a test sample comprising the target protein and a candidate substance; incubating the control sample and the test sample for a period of time and under appropriate conditions to permit binding to the target protein in the control sample; and comparing the amount of antibody-bound target protein in the control sample to the amount of candidate agent bound target protein in the test sample, wherein a candidate agent having at least 40% the amount of bound candidate agent to target protein compared to the amount of bound target protein in the control sample is selected as having sufficient binding/inhibiting activity.
- 2. The method of claim 1 wherein D1 further comprises a first and a second anti-parallel beta-sheet connected to one another by a salt bridge.
- 3. The method of claim 1 wherein the ligand is a homophilic binding domain of CEACAM1, MHV viral spike glycoprotein, Neisseria, or Hemophilus bacteria.
- 4. The method of claim 1 wherein the target protein comprises a cell surface receptor.
- 5. The method of claim 4 wherein the target protein comprises a cell surface protein on an epithelial cell, a leukocyte, an endothelial cell, or a placental cell.
- 6. The method of claim 1 wherein the selected candidate substance inhibits virus binding.
- 7. The method of claim 3 wherein the selected candidate substance inhibits binding of a pathogenic strain of bacteria of Neisseria or Hemophilus.
- 8. The method of claim 7 wherein the pathogenic strain is a Hemophilus strain.
- 9. The method of claim 7 wherein the pathogenic strain of bacteria is a Hemophilus strain.
- 10. The method of claim 1 wherein the selected candidate substance is capable of blocking cell-mediated immune responses.
- 11. The method of claim 1 wherein the selected candidate substance provides a bacterial inhibiting activity.
- 12. The method of claim 10 wherein the selected candidate substance provides a treatment for bacterial infection.
- 13. The method of claim 10 wherein the selected candidate substance provides a treatment for diarrhea.
- 14. The method of claim 10 wherein the selected candidate substance provides a treatment for hepatitis.
- 15. A soluble protein in the CEA family comprising:
a hydrophobic core molecule; a functional CC′ binding domain having a convoluted and protruding structure; and a carboxy terminal D4 containing an elongated CD loop.
- 16. The soluble CEA family protein of claiml4 further defined as having an A-A′ kink comprising a cis-proline amino acid residue.
- 17. The soluble CEA family protein of claim 14 further comprising a detectable molecular tag molecule.
- 18. The soluble CEA family protein of claim 14 further defined as comprising an amino acid sequence of SEQ ID NO: 1.
- 19. The soluble CEA family protein of claim 14 further defined as comprising an amino acid sequence of SEQ ID NO: 2.
- 20. The soluble CEA family protein of claim 14 further defined as comprising an amino acid sequence of SEQ ID NO: 3.
- 21. The soluble CEA family protein of claim 15 further defined as a cellular receptor for a coronavirus.
- 22. A pharmaceutical formulation comprising the molecule of claim 15 in a pharmaceutically acceptable excipient.
- 23. The pharmaceutical formulation of claim 22 further defined as an antiviral agent.
- 24. An antiviral agent comprising a molecule capable of binding with high affinity and under stringent conditions to a target antigen molecule having:
a virus binding domain, D1, having a first and a second anti-parallel beta-sheet connected to one another by a salt bridge, a protruding, convoluted CC′ loop, and an A-A′ kink, a C-terminal domain, D4, having an elongated CD loop, and a flexible linker connecting D1 to D4.
- 25. The antiviral agent of claim 24 wherein the anti-viral agent is further defined as binding to the target antigen molecule with an affinity of about 10(4) to about 10(10).
Government Interests
[0001] The United States Government may own rights to the invention as research relevant to its development was funded by NIH Grants GM56008, HL48675, AI25231, and HL54734.