Tryptic hydrolysis of hGH-RH(1-29)-NH2 analogues containing Lys or Orn in positions 12 and 21.
Witkowska. E E; Orłowska. A A; Sagan. B B; Smoluch. M M; Izdebski. J J
Key Findings
- Both hGH‑RH analogues were synthesized and exposed to trypsin, with degradation tracked by HPLC and mass spectrometry.
- The analogue containing ornithine (instead of lysine) resisted cleavage at the 12‑13 and 21‑22 peptide bonds, making it less susceptible to enzymatic breakdown.
- Replacing lysine with ornithine may be a useful strategy for creating peptides that are more stable in biological fluids.
Practical Outcomes
- For biohackers interested in growth‑hormone‑releasing peptides, using ornithine in place of lysine could lead to a longer‑lasting compound, potentially reducing how often you need to dose. However, the study was done in a test‑tube, so real‑world effectiveness and safety still need to be confirmed before changing any protocols.
Summary
Researchers made two versions of a 29‑amino‑acid growth‑hormone‑releasing peptide and tested how quickly they were broken down by the enzyme trypsin. The version that swapped lysine for the similar amino acid ornithine was much harder for trypsin to cut, especially at two key spots. This shows that small changes in the peptide’s makeup can make it more stable in the body.
Abstract
Two analogues of the 29 amino acid sequence of human growth hormone-releasing hormone, namely [Nle27]hGH-RH(1-29)-NH2 and [Orn(12,21),Nle27]hGH-RH(1-29)-NH2, have been synthesized and subjected to digestion by trypsin. The course of degradation was followed using RP-HPLC and ESI-MS. Several intermediates and final products of degradation were identified and conclusions regarding the rate of cleavages at different positions occupied by Lys and Arg residues were drawn. The analogue containing ornithine was found to be less susceptible to hydrolysis by trypsin: the 12-13 and 21-22 peptide bonds were completely resistant to the cleavage. The results show that by replacing Lys with Orn, a possibility exists to design new peptides, which could be more stable in biological fluids.
Study Information
pubmed
2001
2001-03-01T00:00:00.000Z
10.1002/psc.316
13
19