Intercalator

Intercalator Intercalators are the agents that capable of inserting themselves into the successive base pairs in the DNA, therefore, making the pair of DNA kinking, uncoiling or even deform. This is cause the DNA to be malfunctioned.[1] Intercalators are based on several supramolecular interactions simultaneously operating between the ligand and the particular base pair of the DNA. They usually use the pi-electron stacking or hydrogen bond and Van de Waal force or hydrophobic interaction to insert between the particular base pair of DNA.[2] This is because the DNA is double helix, the twist was made by the hydrogen bond interaction between the base pairs.[3] The intercalator may insert into the gap between the base pair. Usually intercalator are categorized as mutagens or carcinogenic substance. [pic] Definition of Hydrogen bond : when a hydrogen atom is bonded to a highly electronegative atom such as fluorine, oxygen and nitrogen, the bonding electron pair will draw towards the high electronegative atom. As the H atom don’t have inner shell electrons and small in size, the charge density is high. It will expose to attraction by nearby electron cloud, like a lone pair of electrons on an electronegative atom. The electrostatic attraction between the lone pair of electrons on the electronegative atom and the slightly positively charged hydrogen atom is called hydrogen bond.[4] [pic] Why they could cause cancer' They usually replace the original interaction between two base pairs, thus, making the DNA unwind or distorted.[5] Then the DNA will make the messenger RNA miscoding or other kind of DNA failure to cause the wrong replication of cell and the immune system was failed to destroy the abnormal cell.[6] [pic] Ethidium intercalated between two adenine-thymine base pairs. Anti-cancer drugs are a kind of intercalators. They are using the theory of intercalators causing the distortion and unwinding of DNA to kill the abnormal cells. Usually they are acting when the cells are doing the first step of mitosis, replication of chromosomes. There are six types of drugs.[7] • Alkylating agents : Replace hydrogen atom in the oraganic molecules by alkyl groups, especially effective on Guanine. It will make the nucleotides wrong ordered and make the messenger RNA miscoding and break the DNA.[7] • Antimetabolites : inhibit the enzyme-substrate reaction and make the metabolism not work[7] • Antiturmor antibiotics : Similar to alkylating agents which will intercalating with DNA make it not replicable and not able to synthesis messenger RNA, thus, break the DNA.[7] • Other three types are similar to the above. (hormone and hormone antagonists , vinca alkaloid , others[cis-platin , L-asparaginase])[7] [pic] Where the medicines act on and their mechanisms[7] Reference : 1. Intercalators, medical dictionary, http://www.medical-dictionary.cc/what-does/intercalators-mean 2. James Jin and Jung-II Grote , Materials Science of DNA , Pages 49–76 , CRC Press 2011 3. Y.C.Wong, C.T.Wong , New Way Chemistry for Hong Kong A-level book 1 third edition, P.293 , Manhattan Press , 2006 4. Y.C.Wong, C.T.Wong , New Way Chemistry for Hong Kong A-level book 1 third edition, P.287 , Manhattan Press , 2006 5. Loren Dean Williams , Martin Egli , Qi Gao , Alexander Rich , department of biology , Massachusetts Institute of Technology , DNA intercalation : helix unwinding and neighbor-exclusion , P.107-124 http://ww2.chemistry.gatech.edu/~lw26/bPublications/LDW_19.pdf 6. Y.K.Ho, New Way Biology for Hong Kong A-level book 4 , P.394 , Manhattan Press , 2007 7. Liu Shing-Hwa , Basic and Clinical Pharmacology , P.480-496 , Farseeing Publishing Co. Ltd. , 2000 , ISBN : 957-640-194-1