5. ANTIBIOSIS AND ANTIBIOTICS
281
3. Polypeptide Antibiotics*
A large number of antibiotics, mainly from streptomycetes and bacilli,
are typical polypeptides of variable complexity. It is also known that
certain polypeptides from animal tissues and cells have antimicrobial
properties. Such is the case, for instance, for the so-called anthracocidal
agent, which is a basic peptide rich in lysine, and for a fraction from calf
thymus (165b).
Table II shows the products obtained from hydrolysis of some
polypeptide antibiotics. It will be seen that they comprise the amino
acids regularly found in protein hydrolyzates and a few less common
ones, such as lanthionine, ^-methyllanthionine, γ-aminobutyric and α,γdiaminobutyric acids.
Several of the smaller polypeptide antibiotics have been more thoroughly studied; in many cases they were found to be cyclic peptides.
Thus, gramicidins Jl and J2 (XLVI), from Bacillus brems, are, respectively, hexa- and heptacyclopeptides. Gramicidin S (XLVII) and tyrocidins A and Β (XLVIII), the latter two originally found associated with
gramicidin D in the antibiotic complex tyrothricin, are cyclic decapeptides also produced by B. brems. Mycobacillin (XLIX) is a cyclic tridecapeptide from B. subtilis.
In bacitracin A (L), one member of a complex of related antibiotics
and biologically inert compounds (165c) produced by B. subtilis and
B. licheniformis (ayfivin), a hexapeptide is cyclized by an amide bond
between the a-carboxylic group of aspartic acid and the γ-amino group
of lysine. It bears two side chains: one is asparagine, peptidically bound
to lysine; the other is a straight-chain pentapeptide linked to lysine and
with its two terminal amino acids, cysteine and isoleucine, conjugated in
a thiazole ring. Divalent metal ions are necessary for bacitracin activity
(165d). Its mode of action, although in many ways similar to that of
penicillin, is not completely elucidated
(165e).
* In the formulas illustrating Sections 3 and 4, the following abbreviations are
used, in addition to the conventional ones for amino acids:
MeOct: ( + ) -6-methyloctanoic acid;
Dab: α,γ-diaminobutyric acid;
Hiv: α-hydroxyisovaleric acid;
Lac: lactic acid.
Peptide and ester bonds are represented by an arrow, the foot of which locates
the carboxylic group, its head the amino or hydroxyl group, the latter being distinguished by the letter O. Whenever needed, a Greek letter indicates which one of
several identical functional groups is involved.
281
3. Polypeptide Antibiotics*
A large number of antibiotics, mainly from streptomycetes and bacilli,
are typical polypeptides of variable complexity. It is also known that
certain polypeptides from animal tissues and cells have antimicrobial
properties. Such is the case, for instance, for the so-called anthracocidal
agent, which is a basic peptide rich in lysine, and for a fraction from calf
thymus (165b).
Table II shows the products obtained from hydrolysis of some
polypeptide antibiotics. It will be seen that they comprise the amino
acids regularly found in protein hydrolyzates and a few less common
ones, such as lanthionine, ^-methyllanthionine, γ-aminobutyric and α,γdiaminobutyric acids.
Several of the smaller polypeptide antibiotics have been more thoroughly studied; in many cases they were found to be cyclic peptides.
Thus, gramicidins Jl and J2 (XLVI), from Bacillus brems, are, respectively, hexa- and heptacyclopeptides. Gramicidin S (XLVII) and tyrocidins A and Β (XLVIII), the latter two originally found associated with
gramicidin D in the antibiotic complex tyrothricin, are cyclic decapeptides also produced by B. brems. Mycobacillin (XLIX) is a cyclic tridecapeptide from B. subtilis.
In bacitracin A (L), one member of a complex of related antibiotics
and biologically inert compounds (165c) produced by B. subtilis and
B. licheniformis (ayfivin), a hexapeptide is cyclized by an amide bond
between the a-carboxylic group of aspartic acid and the γ-amino group
of lysine. It bears two side chains: one is asparagine, peptidically bound
to lysine; the other is a straight-chain pentapeptide linked to lysine and
with its two terminal amino acids, cysteine and isoleucine, conjugated in
a thiazole ring. Divalent metal ions are necessary for bacitracin activity
(165d). Its mode of action, although in many ways similar to that of
penicillin, is not completely elucidated
(165e).
* In the formulas illustrating Sections 3 and 4, the following abbreviations are
used, in addition to the conventional ones for amino acids:
MeOct: ( + ) -6-methyloctanoic acid;
Dab: α,γ-diaminobutyric acid;
Hiv: α-hydroxyisovaleric acid;
Lac: lactic acid.
Peptide and ester bonds are represented by an arrow, the foot of which locates
the carboxylic group, its head the amino or hydroxyl group, the latter being distinguished by the letter O. Whenever needed, a Greek letter indicates which one of
several identical functional groups is involved.