Ricin - inhibitor design. Annual report, 15 April 1994-14 April 1995
Technical Report
·
OSTI ID:191508
Substrates for ricin A-chain include short RNA stem-loop structures which have been synthesized with radioactive labels for ease of catalytic assay and for kinetic isotope effects. Ricin A-chain from several sources is incapable of completing multiple catalytic cycles using these substrates. A family of ricin substrate analogue molecules have been synthesized and tested which are specific for transition states with oxycarbonium character or for enzymatic mechanisms involving protonation of the adenine leaving group. Formycin analogues were incorporated into RNA oligomeric structures and tested for binding to ricin A-chain or as inhibitors of the ricin-inactivation of in vitro translation using rabbit reticulocyte lysates. Ribo-oxycarbonium ion analogues containing iminoribitol analogues of ribose were synthetically incorporated into RNA oligomeric structures. Neither formycin nor ribo-oxycarbonium analogues, either singly or in RNA oligomers caused significant inhibition of ricin A-chain when assayed in reticulocyte lysate translation assays. The results indicate a novel transition state mechanism for ricin A-chain, or a requirement for additional features of 28s rRNA to bind transition state analogues.
- Research Organization:
- Albert Einstein Coll. of Medicine, Bronx, NY (United States)
- OSTI ID:
- 191508
- Report Number(s):
- AD-A--299338/4/XAB; CNN: Contract DAMD17-93-C-3051
- Country of Publication:
- United States
- Language:
- English
Similar Records
RICIN-inhibitor design. Final report, 15 April 1993-14 April 1996
Transition state analogues in structures of ricin and saporin ribosome-inactivating proteins
Identification and structural analysis of ricin inhibitors. Final report
Technical Report
·
Wed May 01 00:00:00 EDT 1996
·
OSTI ID:415902
Transition state analogues in structures of ricin and saporin ribosome-inactivating proteins
Journal Article
·
Mon Jan 11 23:00:00 EST 2010
· Proc. Natl. Acad. Sci. USA
·
OSTI ID:1006028
Identification and structural analysis of ricin inhibitors. Final report
Technical Report
·
Sat Nov 30 23:00:00 EST 1996
·
OSTI ID:481285