Analogues of the marine immunosuppressant microcolin A: preparation and biological activity.
A series of analogs of the immunosuppressive lipopeptide microcolin A has been prepared and evaluated for in vitro activity in the human and murine two-way mixed lymphocyte reaction. The compounds tested were obtained by semisynthetic modification and chemical degradation of the natural product. The relative potencies of these analogs suggest that the hydroxyproline and 5-methyl-3-pyrrolin-2-one portion of the molecule are important for immunosuppressive activity and that other structural elements may play an ancillary role. Methanolysis of microcolin A also led to a novel immunosuppressive lactone analog.
Koehn
F E
FE
Division of Biomedical Marine Research, Harbor Branch Oceanographic Institution, Inc., Fort Pierce, Florida 34946.
McConnell
O J
OJ
Longley
R E
RE
Sennett
S H
SH
Reed
J K
JK
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D007166:Immunosuppressive Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D009842:Oligopeptides; D011759:Pyrrolidines; C076335:microcolin A