Position 2 and position 2/Ala15-substituted analogs of bovine growth hormone-releasing factor (bGRF) with enhanced metabolic stability and improved in vivo bioactivity.

@article{Kubiak1993Position2A,
  title={Position 2 and position 2/Ala15-substituted analogs of bovine growth hormone-releasing factor (bGRF) with enhanced metabolic stability and improved in vivo bioactivity.},
  author={Teresa M Kubiak and Alan R Friedman and Roger A Martin and A K Ichhpurani and Glenn Alaniz and W H Claflin and M. Goodwin and D L Cleary and Curtis R. Kelly and Ralph Hillman},
  journal={Journal of medicinal chemistry},
  year={1993},
  volume={36 7},
  pages={888-97}
}
In order to prepare GRF analogs with high activity in vivo, a strategy was undertaken to stabilize the peptide to dipeptidylpeptidase IV (DPP-IV), a protease found in plasma which inactivates native human and bovine GRF by cleavage of the Ala2-Asp3 bond. Replacement of the Ala2 residue with Ser, Thr, or Gly in [Leu27]bGRF(1-29)NH2 resulted in peptides greatly stabilized against proteolysis in plasma, but having low inherent GH-releasing activity when tested in bovine pituitary cell cultures… CONTINUE READING