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GSJ: Received June 30 2005:
http://wbabin.net/saba/saba55.htm
Oral Drugs which Direct an Immediate Antibody Response to a Resistant Virus or Cell
James Saba
Addendum 7/6/05 The following paper has just been brought to my attention, and describes precisely what I'm proposing in Figure 1.
Design and synthesis of alphaGal-conjugated peptide
T20 as a novel antiviral agent for
HIV-immunotargeting.
Naicker, KP; Li, H; Heredia, A;
Song, H & Wang, L-X (Univ of Marylang) Org. Biomol.
Chem. 2004 (2):660-664
Interestingly they find that the construct inhibits infection independent of antibody, and almost certainly the efficacy of such inhibitors can be increased by making a multivalent form via conjugating a multitude to a polymer as shown in the following figure, and as described by:
Use of phage display and polyvalency to design
inhibitors of protein-protein interactions.
Mourez M
& Collier, RJ Methods Mol Biol. 2004;261:213-28
If desired, this multiple-ligand-conjugated polymer can be conjugated to other molecules such as toxins or antibody binding haptins.
Provisional claims
2) Claim 1 wherein the infectious agent target is a virion.
It has become clear that an antibody response to an infectious agent, especially HIV, is often ineffective due to inaccessibility of antibody to relatively nonvariable protein sequences (1-4).
Herein is proposed a solution to this dilemma, via the use of 'adapter' molecules as depicted in Figure 1.
,In essence we are extending the reach of an antibody via the adapter molecule, which comprises a target binding moiety (5-16), an antibody-binding haptin such as dinitrophenyl (DNP), and optionally a spacer. Certain adaptors may be orally administered. The conjugation chemistry for synthesizing such adapters is well known, and more complex adapters, for example with multiple target binding moieties and/or haptins are possible.
The method of using such adaptors involves the immunization of an individual with a haptin-conjugated immunogen (17) such that this individual makes antibody to this haptin.
To this immunized individual, prior or subsequent to infection, the appropriate adapter is administered.
Importantly, note the universality of the method, in that the same previously induced anti-haptin antibodies can be used to fight different infectious agents or transformed cells, simply by conjugating the 'universal' haptin to the appropriate target binding ligand.
Various immunosuppression schemes (18-24) can prophylactically prevent any immune response to a particular target ligand, especially when part of an antibody-adaptor complex.
Another embodiment of the present invention, as exemplified in Figure 2, is the use of ligand-directed covalent conjugation of a molecule to a target (25-30), which subsequently effects a cytotoxic T cell response against the target-conjugated molecule.
,For clarity we use the same target as in Figure 1. A simpler version of the ligand-directed alkylator would be to have a reactive moiety as part of the target-binding ligand.
Of course the desired ligand-directed alkylation must be highly specific to the target.
The following provisional claims are an attempt to encompass important aspects of this invention.
2) A set of adaptor molecules, each comprising a different target-binding portion and a common antibody-binding haptin portion.
3) A method of therapy utilizing an adapter molecule as described in claim 1.
4) Methods of therapy for two different diseases utilizing the adaptor molecules described in claim 2.
5) A method of directing a cytotoxic T lymphocyte response to a target, comprising selectively covalently conjugating this target in vivo.
2) A ligand-binding pocket in the dengue virus
envelope glycoprotein.
Modis, et al Proc Natl Acad
Sci U S A. 2003 Jun 10;100(12):6986-91. Epub 2003 May
20.
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Modis, et al Proc Natl Acad
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No abstract available.
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a TLR7/8 Agonist Results in the Generation of HIV-1
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acid designed as affinity ligands for HIV-1 integrase.
Zhang, et al Bioorg Med Chem. 2001 Jul;9(7):1649-57
30) Synthesis of
(+)-cis-N-(4-Isothiocyanatobenzyl)-N-normetazocine, an
Isothiocyanate Derivative of N-Benzylnormetazocine as
Acylant Agent for the 1 Receptor.
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32) Dimeric zanamivir conjugates with various linking
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Use of phage display and polyvalency to design inhibitors of protein-protein interactions.
Mourez M & Collier, RJ Methods Mol Biol. 2004;261:213-28
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It would be a great help if you could tell me if you have ever seen anything like what is described?