RP-1551s, a family of azaphilones produced by Penicillium sp., inhibit the binding of PDGF to the extracellular domain of its receptor.
Nine azaphilones designated RP-1551-1, -2, -3, -4, -5, -6, -7, -M1, and -M2 were isolated from the culture broth of Penicillium sp. SPC-21609 as inhibitors of PDGF binding to its receptor. RP-1551s inhibit the binding of PDGF AA to the extracellular domain of PDGF alpha-receptor with IC50 values ranging from 0.1 to 2 microM without affecting PDGF BB binding to the extracellular domain of PDGF beta-receptor. PDGF binding was not restored after the PDGF alpha-receptor extracellular domain was washed in an attempt to remove the RP-1551-1 bound to the receptor. This result suggests that RP-1551-1 may irreversibly interact with the PDGF alpha-receptor. Since many azaphilone compounds possess high reactivity with an amino group, RP-1551-1 may prevent PDGF AA binding by reacting with amino groups on the alpha-receptor extracellular domain.
Toki
S
S
Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Japan.
Tanaka
T
T
Uosaki
Y
Y
Yoshida
M
M
Suzuki
Y
Y
Kita
K
K
Mihara
A
A
Ando
K
K
Lokker
N A
NA
Giese
N A
NA
Matsuda
Y
Y
D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology*; D001578:Benzopyrans / Q000302:isolation & purification / Q000494:pharmacology*; D003470:Culture Media; D005110:Extracellular Space / Q000378:metabolism; D005285:Fermentation; D006801:Humans; D010407:Penicillium / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011485:Protein Binding; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000378:metabolism
D000900:Anti-Bacterial Agents; D001578:Benzopyrans; D003470:Culture Media; D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; D012710:Serum Albumin, Bovine; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor