Scientists made 25 slightly different versions of the peptide GHRP‑6 to see how tiny changes affect how it sticks to a cell‑surface protein called CD36 and how it influences inflammation and blood‑vessel growth. They found that swapping a few building blocks changes the binding strength (up to 17‑times) and how well the peptide can lower nitric‑oxide production in immune cells or affect tiny blood‑vessel sprouts in eye tissue. The work is mostly a chemistry‑focused proof‑of‑concept, not a ready‑to‑use dosing guide.

Azapeptide analogues of growth hormone releasing peptide-6 (GHRP-6) exhibit promising affinity, selectivity, and modulator activity on the cluster of differentiation 36 receptor (CD36). For example, [A¹, azaF⁴]- and [azaY⁴]-GHRP-6 (1a and 2b) were previously shown to bind selectively to CD36 and exhibited respectively significant antiangiogenic and slight angiogenic activities in a microvascular sprouting assay using choroid explants. The influences of the 1- and 4-position residues on the affinity, anti-inflammatory, and antiangiogenic activity of these azapeptides have now been studied in detail by the synthesis and analysis of a set of 25 analogues featuring Ala¹ or His¹ and a variety of aromatic side chains at the aza-amino acid residue in the 4-position. Although their binding affinities differed only by a factor of 17, the analogues exhibited significant differences in ability to modulate production of nitric oxide (NO) in macrophages and choroidal neovascularization.