Spiramycin, structure

Fig. 4.7 Superposition of macrolides. A cutaway view of a space-filled representation of rRNA (gray) and protein (light blue) show the peptide exit tunnel (left) and the peptidyl transferase center (upper right) of H. maris-mortui. The lactone rings of tylosin (orange sticks), carbomycin A (red sticks), spiramycin (yellow sticks) and azithromycin (light blue sticks) become superimposed when rRNA is superimposed among these structures. The lactone rings bind to the hydrophobic crevice...

The spiramycin family is often classified separately from the leucomycin family despite the close resemblance of their respective aglycones. The spiramycins are structurally distinct in that the 9-a-hydroxyl group of their aglycone is glycosylated by a yff-D-forosaminyl moiety. Having this second amino sugar incorporated into the typical macrolide structure, the spiramycins are unique dibasic macrolides. 

The basic structure of the macrohde antibiotics is characterized by a lactonic cycle with two osidic chains, and they are classified according to the number of carbon atoms in the cycle 14-membered macrohdes (for example clarithromycin, dirithromycin, erythromycin, roxithromycin, troleandomycin), 15-membered macrolides (for example azithromycin), and 16-membered macrolides (for example josamycin, midecamycin, spiramycin). 

The 16-membered macrolide antibiotics are generally classified into two large groups, namely, the leucomycin-related family and the tylosin-related family, on the basis of the substitution patterns of their aglycons (Fig. 28) [187]. Interestingly, the leucomycin series, such as leucomycin, josamycin, midecamycin, and spiramycin, have been used clinically for humans, while the tylosin series has been utilized in veterinary medicine. In this section, we describe recent studies on the chemical modification of 16-membered macrolides and their structure-activity relationships. 

Evidence also indicates that 16-membered-ring macrolides, as peptidyltransferase inhibitors, hinder the polyuridylic acid-dependent polymerization of phenylalanine, despite the fact that 14-membered-ring macrolides are not able to inhibit polyphenylalanine synthesis. In particular, 16-membered-ring macrolides containing at least one disaccharide-monoglycoside in their structures, such as leucomycin, spiramycin, carbomycin, and tylosin, may cause degradation of polyribosome [93,94]. 

These findings are interpreted to indicate that erythromycin resistance mutation in domain II caused an increase in the peptide and disrupted an indirectly functional interaction between domains II and V, because such a mutation could affect alteration of the stability of a secondary rRNA structure (hairpin sequence structure) in domain II. In addition, the Shine-Dalgamo (SD) sequence of the rRNA-encoded E-peptide ORE is sequestered in the hairpin structure. Thereby, SD and E-peptide codon are not accessible to ribosomes of wild-type E. coli. The conformational change of the hairpin structure by erythromycin resistance mutation can be recognized by ribosomes for the initiation of translation of E-peptide. Thus, the increase of the peptide is expected to show resistance to macrolide antibiotics such as erythromycin, oleandomycin, and spiramycin but not clindamycin and chloramphenicol without preventing their binding to the target. 

Therapeutic Function Antibacterial Chemical Name Spiramycin Common Name -Structural Formula ... 

MaerolldM, macrolide antibiotics a group of antibiotics from various strains of Streptomyces, all with the same complex macrocyclic structure. M. inhibit protein synthesis by blocking transpeptidation, and translocation on the 50S ribosomal subunit (similar to Chloramphenicol, see). Examples of M. are erythromycin (Fig.), spiramycin, oleandomycin, carbo-mycin, angolamycin, leucomycin, picromycin. Almost all M. are used therapeutically as broad spectrum antibiotics. 

The Ti-values of the C nuclei have proved extremely helpful in elucidating the structures of monoterpenoid jS-o-glucosides and in analysing the C n.m.r. spectra of macrolide antibiotics (e.g. leucomycin, spiramycin, and chalco-mycin). ... 

Spiramycin is the only one of the macroHdes with a known structure that possesses a 17-membered lactone ling. Structural similarity between magna-... 

Paul, R., et S. Tchelitcheff Structure de la spiramycine. I. Etude des produits de degradation caracterisation du mycarose. Bull. soc. chim. France 1957a, 443. 

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