Conotoxin lt3a was firstly purified and identified from the crude venom of

Conus litteratus

. The proline in the amino acid sequence of lt3a was undergone hydroxylation modification during the process of conotoxin maturation. To investigate the effect of hydroxyproline on the folding and activity of lt3a

conotoxin lt3a［P6O］ with hydroxyproline in position 6 and conotoxin lt3a without hydroxyproline were chemically synthesized and the oxidative folding rate

thermal stability and biological activity of lt3a［P6O］ and lt3a were investigated. The results demonstrated that the hydroxyproline could increase the folding rate of lt3a

but had no effect on thermal stability

which was different from the situation in the collagen. It might be due to the reason that the number of Hyp in lt3a was not enough to form the helix and the stable “water bridge” structure to enhance the thermal stability. Moreover

Hyp substitution had no impact on the conotoxin activity in the case of lt3a.