RP-1776, a novel cyclic peptide produced by Streptomyces sp., inhibits the binding of PDGF to the extracellular domain of its receptor.
RP-1776, a novel cyclic peptide, was isolated from the culture broth of Streptomyces sp. KY11784. RP-1776 selectively inhibited the binding of PDGF BB to the extracellular domain of the PDGF beta-receptor with an IC50 value of 11 +/- 6 microM. Detailed binding experiments suggested that RP-1776 directly interacts with PDGF BB. RP-1776 inhibited the phosphorylation of the PDGF beta-receptor induced by PDGF BB. These results suggested that RP-1776 antagonizes the signaling of PDGF BB probably through the inhibition of PDGF BB binding to the PDGF beta-receptor.
Toki
S
S
Tokyo Research Laboratories, Kyowa Hakko Kogyo Co, Ltd, Japan. stoki@kyowa.co.jp
Agatsuma
T
T
Ochiai
K
K
Saitoh
Y
Y
Ando
K
K
Nakanishi
S
S
Lokker
N A
NA
Giese
N A
NA
Matsuda
Y
Y
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000077214:Becaplermin; D016466:CHO Cells; D006224:Cricetinae; D047630:Depsipeptides; D005285:Fermentation; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D020574:Proto-Oncogene Proteins c-sis; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*; D012988:Soil Microbiology; D013302:Streptomyces / Q000737:chemistry* / Q000378:metabolism
D000900:Anti-Bacterial Agents; D047630:Depsipeptides; D010456:Peptides, Cyclic; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; C075278:platelet-derived growth factor A; C433003:skyllamycins; D000077214:Becaplermin; D017479:Receptors, Platelet-Derived Growth Factor