Bioorganic Chemistry p. 398 - 411 (2003)
Update date:2022-08-16
Topics:
Zheng, Weiping
Cole, Philip A.
Linker modified novel bisubstrate analog inhibitors 4-7 for serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AANAT) have been designed and synthesized. Examination of these inhibitors with AANAT in vitro suggested that: (i) linker hydrogen bonding makes only modest contributions to the affinity of bisubstrate analog inhibitors studied; (ii) greater than or equal to four methylene groups between the indole and the coenzyme A (CoASH) moieties are required for a bisubstrate analog inhibitor to achieve strong AANAT inhibition; (iii) the AANAT active site appears not to accommodate positively charged linkers as well as neutral ones; and (iv) substrate amine pKa depression may constitute one strategy for AANAT substrate recognition and catalysis. The results reported here have enhanced our understanding of AANAT substrate recognition/catalysis, and are important for novel inhibitor design. Since AANAT belongs to the GCN5-related N-acetyltransferase (GNAT) superfamily, our experimental strategies should find applications for other acetyltransferases.
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Doi:10.1021/jo971206u
(1997)Doi:10.1016/S0040-4039(00)70752-0
(1968)Doi:10.1016/0040-4039(96)00692-2
(1996)Doi:10.1002/cssc.201802512
(2019)Doi:10.1002/aoc.4719
(2019)Doi:10.1016/S0014-827X(02)01202-8
(2002)