Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.750557
Title: An investigation into the catalytic mechanism of the adenovirus type II proteinase
Author: Cornish, Julie Anne
Awarding Body: University of St Andrews
Current Institution: University of St Andrews
Date of Award: 1996
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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.
Supervisor: Gani, David Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.750557  DOI: Not available
Keywords: QR456.C7 ; Viral genetics
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