Molecules with O-acetyl group protect protein glycation by acetylating lysine residues

Abstract

Pharmaceutical intervention for reduction of advanced glycation products (AGEs) is considered as a therapeutic strategy to attenuate the pathogenesis of diabetes. Many molecules have been reported to possess antiglycation activity, one such example is acetylsalicylic acid (Aspirin). It protects proteins from glycation by acetylating the lysine residues. Therefore, in this study we have synthesized and screened molecules containing free N-, O-acetyl and acetophenone group. All the selected molecules in this study showed glycation inhibition but interestingly, only molecules with O-acetyl but not Nacetyl and acetophenone group were capable of acetylating lysine residue . Furthermore, we have demonstrated that preacetylation or aspirin treatment prior to the induction of diabetes helps in reducing HbA1c and AGE formation in the streptozotocin induced diabetic mice. Hence pre-acetylation may have an additional therapeutic efficacy of reducing AGE levels in-vivo. Incorporation of O-acetyl group into anti-diabetic molecules could be an useful strategy, as it may have an additive effect in reducing AGEs. Identification of such novel acetylating agents represents a new area in the drug discovery process.

N , N ′-Diacetyl- p -phenylenediamine restores microglial phagocytosis and improves cognitive defects in Alzheimer’s disease transgenic mice

“…Previous studies have indicated the neuroprotective effects of AAP stemming from its effect on the inflammatory pathways in lipopolysaccharide-induced cognitive impairment in mice (29). In addition, in the structure of DAPPD, the additional acetamide functionality could exhibit an improved enzymatic and metabolic stability under physiologically relevant conditions (30,31). Taken together, DAPPD could be an ideal candidate as an antineuroinflammatory compound in vivo.…”

Maillard Proteomics: Opening New Pages

“…Such compounds can be destroyed after enzymatic hydrolysis and removed by SPE afterwards. Currently, several commercial products, delivering reliable and reproducible results are available: anionic acid labile surfactant (AALS) from Progenta [ 53 , 175 ], acid labile RapiGest SF Surfactant from Waters Corporation [ 184 , 185 ]. Additionally, acid cleavable detergents ProteaseMax (Promega) [ 186 ], PPS Silent Surfactant (Expedeon) [ 187 ], and Invitrosol (Invitrogen) [ 188 ] might be used in analysis of post-translationally modified proteins.…”

Development and characterization of two novel 68Ga‐labelled neuropeptide Y short analogues with potential application in breast cancer imaging

“…C2, on the other hand, has an acetyl group bound to the amino group of lysine, resulting in an amide group, which is less reactive under physiological conditions than the original primary amine (Hacker et al., 2017; Vannuruswamy et al., 2016; Zhang et al., 2019). Consequently, the presence of the acetyl group in the linker can explain the apparent disagreement between PPB and lipophilicity of the gallium complexes.…”