1999
DOI: 10.1046/j.1432-1327.1999.00232.x
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Towards minimized gonadotropins with full bioactivity

Abstract: Gonadotropins are highly complex glycoprotein hormones consisting of two noncovalently associated subunits, which are heavily glycosylated. Using the X-ray structure of human choriogonadotropin and structure/activity relationships we aimed to design`minimized' gonadotropins of reduced complexity. Our results show that it is possible to reduce the size of natural human choriogonadotropin by one-third of its molecular weight while retaining its wild-type biopotency. To our knowledge, such`mini'-human choriogonad… Show more

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Cited by 8 publications
(2 citation statements)
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“…The effect of these substitutions on the in vitro bioactivity was highly correlated with their effects on the receptor binding activity. It was repeatedly demonstrated in media and buffers with various salt concentrations, and confirmed by studies in other laboratories ( 25 , 26 ) as well as by using CHO-TSHR cells with largely depleted pool of the negatively charged cell surface proteoglycans. Notably, mutations to alanine did not alter hormone activity, indicating that only selective substitutions to K or R amino acid residues are causing an enhancement of cAMP and IP 3 production, iodine uptake, proliferation of FRTL-5 cells, thyroxine and progesterone production, respectively ( 1 , 21 , 24 ).…”
Section: Charge Cluster In the Common α-Subunitsupporting
confidence: 57%
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“…The effect of these substitutions on the in vitro bioactivity was highly correlated with their effects on the receptor binding activity. It was repeatedly demonstrated in media and buffers with various salt concentrations, and confirmed by studies in other laboratories ( 25 , 26 ) as well as by using CHO-TSHR cells with largely depleted pool of the negatively charged cell surface proteoglycans. Notably, mutations to alanine did not alter hormone activity, indicating that only selective substitutions to K or R amino acid residues are causing an enhancement of cAMP and IP 3 production, iodine uptake, proliferation of FRTL-5 cells, thyroxine and progesterone production, respectively ( 1 , 21 , 24 ).…”
Section: Charge Cluster In the Common α-Subunitsupporting
confidence: 57%
“…( 3 , 38 , 42 , 43 )]. Moreover, largely reduced binding activity and potency of single-chain hCG and its minimized variants were restored using αL1 loop substitutions (α4K and α4R) ( 25 , 26 ). Remarkably, also the LH activity of the hTSH/hCG “seat-belt” “determinant loop” chimera was further increased by concomitant introduction of a cluster of K residues (α4K) into a highly distant from “seat-belt” αL1 13–20 domain ( 41 ).…”
Section: Gph Super-agonists – Tools In Structure–function Studiesmentioning
confidence: 99%