Synthesis of a Novel β-lactamase Hydrolysis Resistant Penicillin Analog

Iyad Ali's picture
Journal Title, Volume, Page: 
Saudi Pharmaceutical Journal ,v.13,No. 2-3,P. 83-88 Saudi Arabia
Year of Publication: 
Iyad A.F. Ali
Faculty of Pharmacy, Applied Science University, Amman, ‎‎11931, Jordan‎
Current Affiliation: 
Faculty of Medicine & Health Sciences, Department of Biomedical Sciences, An-Najah National University, Nablus, Palestine
Nina Sakhnini
Samar Khater
Preferred Abstract (Original): 

It has been suggested that Lys234 residue participates in -lactamase catalysis by acting as an electrostatic anchor for the C-3 carboxylate of penicillin. The aim of the present work is to test the role of the carboxylate group at C-3 in binding with the enzyme. A novel penicillin derivative, 3-aminomethyl-6-phenylacetamidopenicillanate, was prepared in which the carboxylic acid group at C-3 was replaced by an amino group. This was achieved by the reduction of a mixed anhydride of penicillin G to obtain 6-phenylacetamidopenicillanyl alcohol. The behavior of the alcoholic function in reacting with acidic components, following Mitsunobu reaction, was investigated, and 3-di-tert-butoxycarbonylaminomethyl-6-phenylacetamidopenicillanate was prepared as a crude product. After purification using column chromatography, the crude product undergoes deprotection of the amino group to produce the desired compound 3-aminomethyl-6-phenylacetamidopenicillanate. The hydrolysis of this compound by β-lactamase and the altered β-lactamase was determined and studied. The alteration in -lactamase was done by changing the lys234 residue to glutamic acid residue using site specific mutagenesis. 

Synthesis of a Novel β-lactamase Hydrolysis Resistant Penicillin Analog755.99 KB