Category: Chemical Biology
Organophosphates (OPs) are organic esters of phosphoric acid, which are widely used for various industrial and household applications, e.g. as pesticides, plasticizers, flame retardants and solvents. Phosphonates are another class of organophosphorus compounds containing C-PO(OH)2 or C-PO(OR)2 groups (where R = alkyl, aryl). Some highly toxic organophosphates and organophosphonates have also been employed as chemical warfare agents. Those toxic compounds may also be environmentally persistent. Toxicity mainly stems from their efficient inhibition of the enzyme acetylcholinesterase, a crucial enzyme for the regulation of neutral activity. The adverse effects of OP toxins on human health and on the environment demand efficient decontamination strategies. Detoxification may be carried out by physical means (e.g. adsorption, flushing) or by chemical decontamination to more benign products. Hydrolysis often does the latter, either stoichiometrically (e.g. alkaline solutions) or catalytically (e.g. enzymes, transition metal and main group metal complexes, MOFs.)
Our efforts focus in the design of environmentally benign catalytic systems for hydrolytic cleavage of P-O bonds in the decomposition of toxic OPs. Activity probes, activated by the said reaction, were designed and will be implemented to select catalysts using a combinatorial approach based on phage display libraries of short cyclic and acyclic peptides. We intend to scan the phage display libraries for O-P hydrolytic activity both in the absence and in the presence of selected metal atoms. For practical purposes of visualization and isolation, catalyst screening will be performed by activity-based probes including a fluorescent tag such as bimane , linked to a magnetic bead. The process of screening is monitored both in presence and absence of transition metals that have binding affinity towards bimane as reported in our recent paper.1 The main feature of the activity probe is the formation of a covalent bond with the selected P-O cleaving catalyst. The attachment of magnetic bead to the activity-based probe will enable us to separate the phages displaying active peptides bound to the probe simply by using an external magnet. In SLAS 2018 meeting, we shall outline our general strategy for catalyst development, including some preliminary results pertaining to the synthesis of organophosphate activity-probes as well as screening approach using syn-(Me,Me)bimane as a first generation fluorescent tag.
References: 1. P.J.Das, Y. Diskin-Posner, M. Firer, M. Montag, F. Grynszpan.; Dalton Trans. 2016, 45, 17123-17131.
Partha Jyoti Das– Mr., Ariel University, Ariel, Tel Aviv, Israel
Ariel, Tel Aviv, Israel
Partha has an oustanding career as a student in B.Sc ( 7th position holder in Gauhati University, India) and in M.Sc ( 4th position). During his undergraduate year, Partha has recieved prestigious Indian Academy of Sciences summer research fellowship consecutively for two years back in 2012 and 2013. He investigated the total synthesis of Habbemine in IIT, Kharagpur under supervision of Prof. Samik Nanda. In 2013 he perfomed his research expertise in total synthesis of Tamiflu under supervision of Prof. Sanjay Batra in Cental Drug Research Institute, India. His M.Sc thesis on nano catalysed dimedone coupling was financially awarded by Assam Science Technology and Environment Council. In 2015, he moved to Israel for PhD under Prof. Michael Firer and Prof. Flavio Grynszpan in Ariel University where he is involved to investigate detoxification of nerve gas agents. A primary results have been published on the cover page of Dalton Transaction, 2016.