Increased stability of human growth hormone with reduced lactogenic potency.
Human growth hormone (hGH), whose main function is the somatic growth stimulation, induces diverse effects including lactation. We examined the possibility of hGH stabilization by elimination of its lactogenic activity. Chimeric GHs were constructed by replacement of different segments of hGH with sequences derived from non-lactogenic porcine GH. As was observed in the rat Nb2-11C lymphoma cell test, lactogenic activity of some chimeric hormones was seriously destroyed. This kind of hormones displayed the substantial increase in thermal and guanidine hydrochloride stability. The more stable hGH variants were found to be more soluble in Escherichia coli cells.
Schulga
Alexey A
AA
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya St. 17/10, Moscow 117997, Russia.
Makarov
Alexander A
AA
Levichkin
Iliya V
IV
Belousova
Yuliya V
YV
Lobachov
Vladimir M
VM
Protasevich
Irina I
II
Pace
C Nick
CN
Kirpichnikov
Mikhail P
MP
D000818:Animals; D002460:Cell Line; D004355:Drug Stability; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005260:Female; D013006:Growth Hormone / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D019791:Guanidine; D006358:Hot Temperature; D019382:Human Growth Hormone / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D002479:Inclusion Bodies / Q000378:metabolism; D007774:Lactation / Q000187:drug effects; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D012995:Solubility; D013552:Swine
D011993:Recombinant Fusion Proteins; D019382:Human Growth Hormone; D013006:Growth Hormone; D019791:Guanidine