Many researchers seek to introduce selected changes to DNA in a site-specific manner. Analogs of nucleotides and other chemicals were first used to generate localized point mutations.[10] Such chemicals include aminopurine, which induces AT to GC transition,[11] while nitrosoguanidine,[12] bisulfite,[13] and N4-hydroxycytidine may induce GC to AT transition.[14][15] These techniques allow specific mutations to be engineered into a protein; however, they are not flexible with respect to the kinds of mutants generated, nor are they as specific as later methods of site-directed mutagenesis and therefore have some degree of randomness.