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Peptide bond‐forming reagents H OA t and H ATU are not mutagenic in the bacterial reverse mutation test
Author(s) -
Nicolette John,
Neft Robin E.,
Vanosdol Jessica,
Murray Joel
Publication year - 2016
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.21997
Subject(s) - reagent , chemistry , combinatorial chemistry , ames test , drug , peptide bond , in silico , mutagen , peptide , hexafluorophosphate , stereochemistry , biochemistry , pharmacology , salmonella , organic chemistry , bacteria , biology , genetics , ionic liquid , gene , dna , catalysis
The peptide bond‐forming reagents 1‐hydroxy‐7‐azabenzotriazole (HOAt, CAS 39968‐33‐7) and O‐(7‐Azabenzotriazol‐1‐yl)‐N,N,N′,N′‐tetramethyluronium hexafluorophosphate (HATU, CAS 148893‐10‐1) either have structural alerts, unclassified features or are considered out of domain when evaluated for potential mutagenicity with in silico programs DEREK and CaseUltra. Since they are commonly used reagents in pharmaceutical drug syntheses, they may become drug substance or drug product impurities and would need to be either controlled to appropriately safe levels or tested for mutagenicity. Both reagents were tested in the bacterial reverse mutation (Ames) test at Covance, under GLP conditions, following the OECD test guideline and ICH S2(R1) recommendations and found to be negative. Our data show that HOAt and HATU—common pharmaceutical synthesis reagents—are not mutagenic, and can be treated as ordinary drug impurities. Environ. Mol. Mutagen. 57:236–240, 2016. © 2016 Wiley Periodicals, Inc.