290
MAURICE WELSCH
bond between the carboxylic group of an amino acid and the alcohol
group of threonine. The two cyclic peptides may or may not be identical.
SarcL-Pro
SarcL-Pro
/
\
/
\
L-iV-Meval
D-a-Ileu
L-iV-Meval
D-a-Heu
^L-Threo/
°^L-Threo
/
Actinocinin'
Actinomycin C 3
(LLX)
Actinomycin D, which differs from actinomycin C 3 only in that
D-valine replaces D-alloisoleucine, has been rather extensively used as an
anticancer agent. Its mode of action has therefore been especially studied. According to some authors, this antibiotic acts primarily on deoxyribonucleic acid (DNA), to which it can be specifically bound (184a,b),
since it inhibits the production of a DNA-containing, but not of a
RNA-containing, virus (185) and the DNA-dependent synthesis of RNA
in a cell-free system, this effect being reversed by the addition of DNA
(186a,b). However, according to others, its fundamental action would be
the inhibition of RNA synthesis (187), more precisely of the incorporation of guanine nucleotides (188a). In any case, its long-known inhibitory
effect upon protein biosynthesis might be explained as an indirect consequence of a biochemical lesion occurring on the metabolic pathway of
either one of the nucleic acids. Actinomycin seems to inhibit the maturation of coliphage T2, but not the synthesis of its nucleic and protein
moieties
(188b).
Simpler derivatives (189) and synthetic analogs (190) of the actinomycins are actively investigated as potential anticancer agents.
A lactone ring similar to that of actinomycins occurs in echinomycin
(LX), from S. echinatus, which is a typical representative of a group of
streptomycete polypeptide antibiotics containing a quinoxaline moiety
and comprising actinoleukin (S. aureus), levomycin, antibiotic F-43, the
quinomycins, and the triostins
(191-193).
It is also observed in other streptomycete-produced antibiotics: etamycin or viridogrisein (LXI), from S. griseus, S. lavendulae, S. griseoviridus, possibly the related pyridomycin (S. pyridomyceticus), and the
Β members of the staphylomycin complex, namely, staphylomycin S
(LXII), from S. virginiae, ostreogrycins B, Bi, B 2 , and B 3 , from S. ostreogriseus, mikamycin B, from S. mitakaensis, antibiotics PA-114-B1 and
PA-114-B3, from S. olivaceus.
MAURICE WELSCH
bond between the carboxylic group of an amino acid and the alcohol
group of threonine. The two cyclic peptides may or may not be identical.
SarcL-Pro
SarcL-Pro
/
\
/
\
L-iV-Meval
D-a-Ileu
L-iV-Meval
D-a-Heu
^L-Threo/
°^L-Threo
/
Actinocinin'
Actinomycin C 3
(LLX)
Actinomycin D, which differs from actinomycin C 3 only in that
D-valine replaces D-alloisoleucine, has been rather extensively used as an
anticancer agent. Its mode of action has therefore been especially studied. According to some authors, this antibiotic acts primarily on deoxyribonucleic acid (DNA), to which it can be specifically bound (184a,b),
since it inhibits the production of a DNA-containing, but not of a
RNA-containing, virus (185) and the DNA-dependent synthesis of RNA
in a cell-free system, this effect being reversed by the addition of DNA
(186a,b). However, according to others, its fundamental action would be
the inhibition of RNA synthesis (187), more precisely of the incorporation of guanine nucleotides (188a). In any case, its long-known inhibitory
effect upon protein biosynthesis might be explained as an indirect consequence of a biochemical lesion occurring on the metabolic pathway of
either one of the nucleic acids. Actinomycin seems to inhibit the maturation of coliphage T2, but not the synthesis of its nucleic and protein
moieties
(188b).
Simpler derivatives (189) and synthetic analogs (190) of the actinomycins are actively investigated as potential anticancer agents.
A lactone ring similar to that of actinomycins occurs in echinomycin
(LX), from S. echinatus, which is a typical representative of a group of
streptomycete polypeptide antibiotics containing a quinoxaline moiety
and comprising actinoleukin (S. aureus), levomycin, antibiotic F-43, the
quinomycins, and the triostins
(191-193).
It is also observed in other streptomycete-produced antibiotics: etamycin or viridogrisein (LXI), from S. griseus, S. lavendulae, S. griseoviridus, possibly the related pyridomycin (S. pyridomyceticus), and the
Β members of the staphylomycin complex, namely, staphylomycin S
(LXII), from S. virginiae, ostreogrycins B, Bi, B 2 , and B 3 , from S. ostreogriseus, mikamycin B, from S. mitakaensis, antibiotics PA-114-B1 and
PA-114-B3, from S. olivaceus.