amino acid sequence substitutional variants are those that have at least one amino acid residue in a native sequence removed and a different amino acid inserted in its place at the same position the substitutions may be single where only one amino acid in the molecule has been substituted or they may be multiple where two or more amino acids have been substituted in the same molecule substitutes for an amino acid within the sequence may be selected from other members of the class to which the amino acid belongs for example the nonpolar hydrophobic amino acids include alanine leucine isoleucine valine proline phenylalanine tryptophan and methionine the polar neutral amino acids include glycine serine threonine cysteine tyrosine asparagine and glutamine the positively charged basic amino acids include arginine lysine and histidine the negatively charged acidic amino acids include aspartic acid and glutamic acid also included within the scope of the invention are proteins or fragments or derivatives thereof which exhibit the same or similar biological activity and derivatives which are differentially modified during or after translation e g by glycosylation proteolytic cleavage linkage to an antibody molecule or other cellular ligand and so on insertional variants are those with.