Integramides A and B, two novel non-ribosomal linear peptides containing nine C(alpha)-methyl amino acids produced by fungal fermentations that are inhibitors of HIV-1 integrase.
[structure: see text]. Integramides A and B are two novel 16-mer linear peptides rich in C(alpha)-methyl amino acids that were isolated from fungal extracts of Dendrodochium sp. by employing a bioassay-guided isolation procedure using recombinant HIV-1 integrase. The structure and stereochemistry were elucidated by a combination of 2D NMR and ESI- and FAB-MS including MS/MS studies and by Marfey's method. Integramides A and B inhibited the coupled reaction of HIV-1 integrase with IC50 values of 17 and 10 microM, respectively.
Singh
Sheo B
SB
Merck Research Laboratories, Rahway, New Jersey 07065, and West Point, Pennsylvania 19486, USA. sheo_singh@merck.com
Herath
Kithsiri
K
Guan
Ziqiang
Z
Zink
Deborah L
DL
Dombrowski
Anne W
AW
Polishook
Jon D
JD
Silverman
Keith C
KC
Lingham
Russell B
RB
Felock
Peter J
PJ
Hazuda
Daria J
DJ
D002851:Chromatography, High Pressure Liquid; D005285:Fermentation; D005658:Fungi / Q000378:metabolism; D019427:HIV Integrase / Q000737:chemistry*; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis*; D009842:Oligopeptides / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*
D019428:HIV Integrase Inhibitors; D009842:Oligopeptides; D010455:Peptides; C456979:integramide A; C456980:integramide B; D019427:HIV Integrase