Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.349249
Title: Studies on the biosynthesis of penicillins
Author: Thomson, Gordon A.
ISNI:       0000 0001 3532 3916
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1984
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Abstract:
A high yielding synthesis of the acyclic precursor of the penicillins, δ- (L-α-aminoadipyl)-L-cysteinyl-D- valine (LLD-ACV) was developed. Using this synthesis the isotopically enriched ACV peptides, δ-(DL-α-aminoadipyl)-L-cysteinyl-D- (3R)- [4-¹ ³C]-valine and δ-(L-α - aminoadipyl)-L- [3-¹ ³c]-cysteinyl-D- [¹ ³N]-valine were prepared. In an extension to this work the tetrapeptide, δ- (L-α-aminoadipyl)- L- cysteinyl-D- valylglycine (LLD-ACVG) was prepared. A putative intermediate in the biosynthesis of isopenicillin N, N- [δ- (L-α-aminoadipyl)-L-cysteinyl ]-N-hydroxy-D-valine (LLD-AC( N-OH) V), was synthesised from N-hydroxy-D-valine benzyl ester. A cell-free system capable of converting δ- (L-α-aminoadipyl )-L- cysteinyl-D-valine to isopenicillin N was obtained from cultures of the cephalosporin producing fungus Cephalosporium acremonium CW19. The cell-free system was used to test the importance of the above synthesised compounds in penicillin biosynthesis. N- [ δ- (L-α-aminoadipyl )-L-cysteinyl ]-N-hydroxy-D-valine was shown not to be a substrate for the enzyme "isopenicillin N synthetase" but to be a potent inhibitor of the LLD-ACV to isopenicillin N conversion. The tetrapeptide, δ- (L-α-aminoadipyl )-L-cysteinyl-D-valylglycine, was found to be a weak inhibitor of this conversion. The isotopically enriched ACV peptides were used to confirm the stereochemistry of the valine C3 centre in biosynthesised δ- (L-α- aminoadipyl)-L-cysteinyl-D-valine and to allow preliminary ¹ ³C n.m.r. studies on the biosynthesis of isopenicillin N.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.349249  DOI: Not available
Keywords: Pharmacology & pharmacy & pharmaceutical chemistry
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