carbodiimide activation via o acylisourea formation followed by subsequent derivatisation for example to a corresponding amide sulphydryl groups may be modified by methods such as carboxymethylation with iodoacetic acid or iodoacetamide performic acid oxidation to cysteic acid formation of a mixed disulphides with other thiol compounds reaction with maleimide maleic anhydride or other substituted maleimide formation of mercurial derivatives using 4 chloromercuribenzoate 4 chloromercuriphenylsulphonic acid phenylmercury chloride 2 chloromercuric 4 nitrophenol and other mercurials carbamoylation with cyanate at alkaline ph tryptophan residues may be modified by for example oxidation with n bromosuccinimide or alkylation of the indole ring with 2 hydroxy 5 nitrobenzyl bromide or sulphenyl halides tyrosine residues on the other hand may be altered by nitration with tetranitromethane to form a 3 nitrotyrosine derivative modification of the imidazole ring of a histidine residue may be accomplished by alkylation with iodoacetic acid derivatives or n carbethoxylation with diethylpyrocarbonate examples of incorporating unnatural amino acids and derivatives during peptide synthesis include but are not limited to use of norleucine 4 amino butyric acid 4 amino 3 hydroxy 5 phenylpentanoic acid 6 aminohexanoic acid t butylglycine norvaline phenylglycine ornithine sarcosine 4 amino 3 hydroxy 6 methylheptanoic acid 2 thienyl alanine and or d isomers of amino acids non naturally occurring amino acids contemplated.