Details
| Original language | English |
|---|---|
| Pages (from-to) | 2022-2034 |
| Number of pages | 13 |
| Journal | Journal of the Chemical Society. Perkin Transactions 1 |
| Volume | 1 |
| Issue number | 17 |
| Publication status | Published - 1 Jan 2001 |
| Externally published | Yes |
Abstract
Mechanism based inhibitors of diaminopimelate aminotransferase (DAP-AT) were designed using knowledge of its substrate specificity and mechanism. Synthesis of thiolester and amide substrate analogues was achieved prior to in vitro inhibition studies, but ester analogues proved too unstable to isolate. Thia substrate analogues showed no inhibitory properties, but the aza substrate analogue 12a showed reversible inhibition vs. DAP-AT and time dependent inhibition in the absence of the natural substrate 4. Substrate analogue 12a is the first example of an amide inhibitor of PLP dependent enzymes. Antibiotic properties of 12a were also briefly assessed.
ASJC Scopus subject areas
- Chemistry(all)
- General Chemistry
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In: Journal of the Chemical Society. Perkin Transactions 1, Vol. 1, No. 17, 01.01.2001, p. 2022-2034.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Synthesis and in vitro enzyme activity of aza, oxa and thia derivatives of bacterial cell wall biosynthesis intermediates
AU - Cox, Russell J.
AU - Wang, Paul S.H.
PY - 2001/1/1
Y1 - 2001/1/1
N2 - Mechanism based inhibitors of diaminopimelate aminotransferase (DAP-AT) were designed using knowledge of its substrate specificity and mechanism. Synthesis of thiolester and amide substrate analogues was achieved prior to in vitro inhibition studies, but ester analogues proved too unstable to isolate. Thia substrate analogues showed no inhibitory properties, but the aza substrate analogue 12a showed reversible inhibition vs. DAP-AT and time dependent inhibition in the absence of the natural substrate 4. Substrate analogue 12a is the first example of an amide inhibitor of PLP dependent enzymes. Antibiotic properties of 12a were also briefly assessed.
AB - Mechanism based inhibitors of diaminopimelate aminotransferase (DAP-AT) were designed using knowledge of its substrate specificity and mechanism. Synthesis of thiolester and amide substrate analogues was achieved prior to in vitro inhibition studies, but ester analogues proved too unstable to isolate. Thia substrate analogues showed no inhibitory properties, but the aza substrate analogue 12a showed reversible inhibition vs. DAP-AT and time dependent inhibition in the absence of the natural substrate 4. Substrate analogue 12a is the first example of an amide inhibitor of PLP dependent enzymes. Antibiotic properties of 12a were also briefly assessed.
UR - http://www.scopus.com/inward/record.url?scp=0035823673&partnerID=8YFLogxK
U2 - 10.1039/b105117m
DO - 10.1039/b105117m
M3 - Article
AN - SCOPUS:0035823673
VL - 1
SP - 2022
EP - 2034
JO - Journal of the Chemical Society. Perkin Transactions 1
JF - Journal of the Chemical Society. Perkin Transactions 1
SN - 1472-7781
IS - 17
ER -