Historical text by DatBTrue, written between 2008 and 2016 and reproduced verbatim. It records what was argued then; it is not dosing guidance and not medical advice. Read the disclaimer.

NOTE that native GRF(1-29) is native GHRH or GRF(1–44) with the inactive final 15 amino acids removed.

It is very important to use ONLY modified GRF(1-29) w/ the four amino acid substitutions as discussed before and NOT unmodified GRF(1-29) Enhanced stability and potency of novel growth hormone-releasing factor (GRF) analogues derived from rodent and human GRF sequences, Robert M. Campbell, Peptides Volume 15, Issue 3, 1994, Pages 489-495

Native human GRF(1–44)-NH2 (hGRF44) is subject to biological inactivation by both enzymatic and chemical routes. In plasma, hGRF44 is rapidly degraded via dipeptidylpeptidase IV (DPP-IV) cleavage between residues Ala [at the 2nd position] and Asp [at the 3rd position]. The hGRF44 is also subject to chemical rearrangement [at the 8th position] and oxidation [at the 27th position] in aqueous environments, greatly reducing its bioactivity.

It is therefore advantageous to develop long-acting GRF analogues using specific amino acid replacements at the amino-terminus [2nd position] (to prevent enzymatic degradation): residue 8 (to reduce isomerization) and residue 27 (to prevent oxidation). Inclusion of Ala [at the 15th position] substitution for Gly, previously demonstrated to enhance receptor binding affinity, would be predicted to improve GRF analogue potency.

In vitro, these analogues were approximately threefold more potent than hGRF44, whereas in vivo they were eleven- to thirteenfold more potent. As the in vitro results reflect only receptor affinity and signal transduction, the increment in potency observed in vivo is likely due to the increased biological half-life of these analogues (i.e., the result of decreased enzymatic and chemical decomposition such that more bioactive peptide is available per unit time). So these changes are made to reduce enzymatic cleavage, amino rearrangement and oxidation in plasma.

In addition “Ala [position] 15-substitution (for Gly) displayed 4–5 times higher affinity for the GRF receptor relative to hGRF(1–44)-NH2…and hence potency.” – GRF analogs and fragments: Correlation between receptor binding, activity and structure, Robert M. Campbel, Peptides Volume 12, Issue 3, May-June 1991, Pages 569-574

[Diagram not preserved: it lived in a forum attachment that was not archived.]

So the above highlighted amino acids need to be modified to:

2nd position – D-Ala 8th position – Gln 15th position – Ala 27th position – Leu