Optimization of an α-aminonaphthylmethylphosphonic acid inhibitor of purple acid phosphatase using rational structure-based design approaches

Feder, Daniel; Mohd-Pahmi, Siti Hajar; Adibi, Hadi; Guddat, Luke W.; Schenk, Gerhard; McGeary, Ross P.; Hussein, Waleed M.

doi:10.1016/j.ejmech.2023.115383

Cited by 1 publication

(2 citation statements)

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“…A growing number of members of the large family of binuclear metallohydrolases have also emerged as targets for chemotherapeutics to treat a diverse range of human disorders 89 . Specifically, elevated levels of PAP activity in osteoclasts are indicative of an osteoporotic phenotype and consequently human PAP is a current target for the development of novel drugs to treat osteoporosis 89 , 90 . Using a combination of fragment-based screening and rational design inhibitors for PAP have been developed with inhibition constants in the nM range 89 , 90 .…”

Section: Applications Of Acid Phosphatasesmentioning

confidence: 99%

“…Specifically, elevated levels of PAP activity in osteoclasts are indicative of an osteoporotic phenotype and consequently human PAP is a current target for the development of novel drugs to treat osteoporosis 89 , 90 . Using a combination of fragment-based screening and rational design inhibitors for PAP have been developed with inhibition constants in the nM range 89 , 90 . These inhibitors are selective for the active site of PAPs but are not yet soluble enough to be considered as suitable drug leads.…”

Section: Applications Of Acid Phosphatasesmentioning

confidence: 99%

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The multifaceted nature of plant acid phosphatases: purification, biochemical features, and applications

Sharma,

Kahandal,

Kanagare

et al. 2023

Journal of Enzyme Inhibition and Medicinal Chemistry

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Acid phosphatases (EC 3.1.3.2) are the enzymes that catalyse transphosphorylation reactions and promotes the hydrolysis of numerous orthophosphate esters in acidic media, as a crucial element for the metabolism of phosphate in tissues. Inorganic phosphate (Pi) utilisation and scavenging, as well as the turnover of Pi-rich sources found in plant vacuoles, are major processes in which intracellular and secretory acid phosphatases function. Therefore, a thorough understanding of these enzymes’ structural characteristics, specificity, and physiochemical properties is required to comprehend the function of acid phosphatases in plant energy metabolism. Furthermore, acid phosphatases are gaining increasing importance in industrial biotechnology due to their involvement in transphosphorylation processes and their ability to reduce phosphate levels in food products. Hence, this review aims to provide a comprehensive overview of the purification methods employed for isolating acid phosphatases from diverse plant sources, as well as their structural and functional properties. Additionally, the review explores the potential applications of these enzymes in various fields.

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