We previously described a pH-sensitive phosphoramidate linker scaffold that can be tuned to release amine-containing drugs at various pH values. In these previous studies it was determined that the tunability of this linker was dependent upon the proximity of an acidic group (e.g., carboxylic acid or pyridinium). In this study, we confirmed that the tunability of pH-triggered amine-release was also dependent upon the pKa of the proximal acidic group. A series of 2-carboxybenzyl phosphoramidates was prepared in which the pKa of the proximal benzoic acid was predictably attenuated by substituents on the benzoate ring consistent with their σ-values.
We previously described a pH-sensitive phosphoramidate linpan>ker scaffold that canpan> be tuned to release pan> class="Chemical">amine-containing drugs at various pH values. In these previous studies it was determined that the tunability of this linker was dependent upon the proximity of an acidic group (e.g., carboxylic acid or pyridinium). In this study, we confirmed that the tunability of pH-triggered amine-release was also dependent upon the pKa of the proximal acidic group. A series of 2-carboxybenzyl phosphoramidates was prepared in which the pKa of the proximal benzoic acid was predictably attenuated by substituents on the benzoate ring consistent with their σ-values.
Authors: Cindy J Choy; Corinne R Ley; Austen L Davis; Brian S Backer; Jonathan J Geruntho; Brian H Clowers; Clifford E Berkman Journal: Bioconjug Chem Date: 2016-09-02 Impact factor: 4.774
Authors: Anthony J Kirby; Daniel W Tondo; Michelle Medeiros; Bruno S Souza; Jacks P Priebe; Marcelo F Lima; Faruk Nome Journal: J Am Chem Soc Date: 2009-02-11 Impact factor: 15.419
Authors: Feyisola P Olatunji; Jacob W Herman; Brittany N Kesic; Damilola Olabode; Clifford E Berkman Journal: Tetrahedron Lett Date: 2020-08-29 Impact factor: 2.415