Somatostatin is a natural inhibitor of
growth hormone, and its analogues are clinically used for the
therapy of
acromegaly,
gigantism, thyrotropinoma, and other
carcinoid syndrome. However, natural
somatostatin is limited for clinical usage because of its short half-life in vivo.
Albumin fusion technology was used to construct long-acting fusion
proteins, and Pichia pastoris was used as an expression system. Three fusion
proteins, (somatostatin (SS)14)2-human
serum albumin (HSA), (SS14)3-HSA, and HSA-(SS14)3, were constructed with different fusion copies of
somatostatin-14 and fusion orientations. The expression level of (SS14)3-HSA and HSA-(SS14)3 was much lower than (SS14)2-HSA due to the additional fusion of the
somatostatin-14 molecule. Matrix-assisted
laser desorption ionization-time-of-flight mass spectrometry revealed that severe degradation occurred in the fermentation process. Similar to the standard of
somatostatin-14, all three fusion
proteins were able to inhibit
growth hormone secretion in the blood, with (SS14)2-HSA being the most effective one. On the whole, (SS14)2-HSA was the most effective
protein in both production level and bioactivity, and increasing the number of small
protein copies fused to HSA may not be a suitable method to improve the
protein bioactivity.