All Submissions | J. Saba Submissions | Physics Site Links | Home Page

Email: James Saba

GSJ: Received Jul. 12, 2005: http://wbabin.net/saba/saba56.htm

'Combinatorial' Epitope Formed by a Ligand and its Target Binding Site

James Saba

Allosteric modulation of a target by a ligand was previously proposed as a means of forming new epitopes (1). However, allosteric modification is not necessary for ligand-dependent formation of a new epitope. Particularly, the molecular contour of a ligand bound to a site on a target may be distinct from both the ligand and target, and thus specifically recolonized by an appropriate antibody (2).

In Figure 1 we are identifying a ligand which binds in a noncovalent or covalent fashion to the target, preferably at a conserved site. Other means of identifying such ligands are conceivable, for example the target could be affixed to a support and bound ligands identified with mass spectrometry.

Once one or more ligands are identified, they can be combined with the target in various ways.

For example, one can fabricate a support-affixed target-ligand complex, and then use this as a means of screening a phage antibody display library as shown in Figure 2.

Other encoded libraries, such as cis-display and cell display libraries are applicable.

Once identified, bound phage, or derivative thereof, could be utilized in conjugation with ligand in scientific investigations, diagnostic assays or therapies. It would also be useful in identifying mimotopes useful as vaccines.

Finally, a soluble target-ligand complex, or a multitude thereof on a virion or particle, would likely be valuable as a vaccine in the induction of broadly neutralizing combinatorial epitope-specific antibodies.

This invention is at present only a concept and it is hoped that others with laboratory facilities will investigate its full potential. Perhaps even establishing collaboration with the inventor. While a US patent application is anticipated, the invention was intentionally published prior to filing such that whatever is novel and useful is now free to much of the world.

The following provisional claims are an attempt to encompass important aspects of this invention.

1) An 'combinatorial' epitope recognized by an antibody (or derivative thereof) and formed by a ligand and its target binding site.

2) An antibody (or derivative thereof) which specifically recognizes the combinatorial epitope of claim 1.

3) Use of a microarray and/or encoded library in the identification of an antibody of claim 2.

4) A method of therapy or vaccine derivation using the antibody of claim 2.

5) A vaccine comprising the combinatorial epitope of claim 1.

References

1) Allosteric Exposure of Sequestered HIV Epitopes.
Saba, JA Gen Sci J 2005 July 9

2) Molecules Which Only Recognize Ligand-Bound Receptors (see Figure 3).
Saba, JA Gen Sci J 2005 June 5

------

It would be a great help if you could tell me if you have ever seen anything like what is described?