Wisconsin Alumni Research Foundation

Michael E Solomon

Daniel H Rich

Disclosed are conjugates of A&bgr;-binding peptides and CsA analogs and conjugates of A&bgr;-binding peptides and FK506 Binding Peptide inhibitors. These conjugates chemically induce dimerization of either cyclophilin or FK506 Binding Peptide with A&bgr; peptide, a major component of amyloid plaques found in neurological disorders such as Alzheimer's disease, multiple sclerosis, and amyotrophic lateral sclerosis. The conjugates are useful in the treatment of neurological diseases involving the formation of amyloid plaques because they inhibit and/or prevent the aggregation and deposition of A&bgr; peptide into plaques.

Cyclosporin a conjugates and uses therefor

Disclosed are cyclosporin analogs having amino acid residue substitutions at positions 1, 3, or 7 of the cyclosporin peptide backbone. Also disclosed are conjugates of these cyclosporin analogs in which an HIV protease inhibitor moiety is conjugated to the position-7 amino acid residue of the cyclosporin. These compounds simultaneously bind to and inhibit cyclophilin and HIV protease. The compounds have good bioavailability and potent HIV inhibitory activity. They are useful in the treatment and prevention of HIV-mediated disorders, including AIDS.

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Arlington, MA, United States of America

Michael E Solomon