Molecular design and prediction of bioactivity of chimeric calcitonin

Objective:To design one new type of calcitonin(CT) analogue with higher bioactivity but lower side-effects.Methods: According to the principle of bioactive peptide drug design and previous work experience,an assumption was raised that bioactivity of new type of calcitonin can be improved by increasing isoelectric point(pI),N-terminal hydrophobicity and C-terminal hydrophilicity of calcitonin molecules.Based on human and salmon calcitonin,a large number of calcitonin analogues were designed and then analyzed in sequence with the help of protein analysis software.The contradictions between activities and side-effects were taken into account and a new type of calcitonin analogue to meet the requirements was determined.Results: Calcitonin analogue meeting bioactivity requirements was chimeric calcitonin of human and salmon calcitonin.Structure prediction showed that the molecular conformation of new calcitonin analogue was similar to salmon calcitonin(sCT).The isoelectric point of chimeric calcitonin analogue was between human and salmon calcitonin.The N-terminal hydrophobicity of new calcitonin analogue was increased more than that of human calcitonin(hCT) and as same as that of salmon calcitonin.Its C-terminal hydrophilicity was as same as that of salmon calcitonin and increased with a high degree compared with human calcitonin.Conclusion:The activity of new calcitonin analogue was predicted to have higher bioactivity than that of human calcitonin,while the side-effects was lower than that of salmon calcitonin.