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An investigation into the catalytic mechanism of the adenovirus type II proteinase
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dc.contributor.advisor | Gani, D. (David) | |
dc.contributor.author | Cornish, Julie Anne. | |
dc.coverage.spatial | 278 p. | en_US |
dc.date.accessioned | 2018-06-12T10:10:31Z | |
dc.date.available | 2018-06-12T10:10:31Z | |
dc.date.issued | 1996 | |
dc.identifier.uri | https://hdl.handle.net/10023/13939 | |
dc.description.abstract | A series of P4 (Cbz and t-Boc) N-protected potential substrates and inhibitors, containing the P1 to P4 substrate recognition sequence of the type 2 adenovirus proteinase (Leu-Ala-Gly-Gly) were prepared by solution phase peptide coupling techniques and tested for activity against the proteinase. The potential substrates contained the amide and ester moieties at the P1 carbonyl position and the potential inhibitors contained the alcohol, acid, bromide, aldehyde, ketone, dimethylacetal, nitrile, alkenic, malonyl and epoxysuccinate moieties at the P1 carbonyl position. The esters, the t-Boc urethane and the p-nitroanilide moieties were substrates for the proteinase and the acid and the amides did not bind to the proteinase. Preliminary results show that the other inhibitors were mostly noncompetitive inhibitors for the adenovirus proteinase with approximate Ki's between 15 and 200 µmol dm-3. The test results indicate that the amides must contain a carbonyl group at P2' to bind to the proteinase; the loss of the P1' amine product is the rate limiting step for the hydrolysis of a substrate by the adenovirus proteinase; the P acid product leaves before the P' amine product, which is in complete contrast to classical cysteine proteinases such as papain; little protonation of the P1'amide nitrogen or the P1 carbonyl oxygen of the adenovirus proteinase-substrate complex occurs before the nucleophilic attack on the P1 carbonyl carbon of the adenovirus proteinase-substrate complex. | en_US |
dc.language.iso | en | en_US |
dc.publisher | University of St Andrews | |
dc.subject.lcc | QR456.C7 | |
dc.subject.lcc | Viral genetics | en |
dc.title | An investigation into the catalytic mechanism of the adenovirus type II proteinase | en_US |
dc.type | Thesis | en_US |
dc.type.qualificationlevel | Doctoral | en_US |
dc.type.qualificationname | PhD Doctor of Philosophy | en_US |
dc.publisher.institution | The University of St Andrews | en_US |
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