Influence of quinone methide reactivity on the alkylation of thiol and amino groups in proteins: studies utilizing amino acid and peptide models

Quinone Methides and their Prodrugs: A Subtle Equilibrium Between Cancer Promotion, Prevention, and Cure

“…The reactivity of QMs is dependent on their stability, and these can alkylate proteins at different sites, for example, at CYS residues or amino groups, particularly the N of the Nterminal residue, the N of LYSs or the amino groups of guanines. This has been shown with BHT-QM (46), the decreasing reactivity order of which is the following: thiols > terminal protein amino groups > LYS = HIS [83]. Such reactivity between QM and biological nucleophiles can be viewed as a reaction between soft and hard species.…”

Characterization of HKI-272 Covalent Binding to Human Serum Albumin

“…However, it is generally considered that Michael reactivity is not efficient for the amino group of lysine reacting with ␣,␤-unsaturated amide because the amino group is a hard nucleophile, whereas the ␣,␤-unsaturated amide is a soft electrophile. Bolton et al (1997) used AA and peptide models to study the influence of paraquinone methide reactivity on the alkylation of thiol and amino groups in protein. Their results indicated that peptide alkylation should occur in the order of cysteine thiol Ͼ N␣-terminal amino Ͼ N-lysine based on chemical reactivity .…”

Targeting molecular signaling pathways of Schistosoma haemotobium infection in bladder cancer

“…It is known from the literature that estradiol is mainly metabolised by (1) oxidation of the hydroxyl function at the C17 position (via steroid dehydrogenase) to yield estrone and (2) hydroxylation via cytochrome P450 enzymes, occurring preferentially on C2, C4 and C16. 81,82 When hydroxylation takes place on the steroid aromatic ring A, catechol-estrogens are produced. 83 Furthermore, the proposed molecular structure of these new estrogenic molecules explains the cellular effects of Sh demonstrated previously in reference 26.…”