Synthesis and neurotrophic activity of nonimmunosuppressant cyclosporin A derivatives.
In order to exploit cyclophilin as a potential target for neurological drug design, we demonstrate in this presentation that several nonimmunosuppressant analogues of cyclosporin A, modified at the various positions in the 'effector' domain, are equipotent nerve growth agents compared to cyclosporin A. Our results suggest that neurotrophic activity of cyclosporin A and its derivatives resides in the binding domain, and binding to cyclophilin and/or inhibiting rotamase activity may be a necessity for neurotrophic effects of cyclophilin ligands.
Wei
Ling
L
Department of Research, Guilford Pharmaceuticals Inc., 6611 Tributary Street, Baltimore, MD 21224, USA.
Steiner
Joseph P
JP
Hamilton
Gregory S
GS
Wu
Yong-Qian
YQ
D000595:Amino Acid Sequence; D000818:Animals; D002645:Chickens; D016572:Cyclosporine / Q000138:chemical synthesis* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000138:chemical synthesis* / Q000235:genetics / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D009414:Nerve Growth Factors; D016572:Cyclosporine