Synthesis and biological activities of β-chain fragments of hemoglobin

To investigate the angiotensin I-converting enzyme (ACE) inhibitory activity of β-chain hemoglobin fragments, 17 fragments were synthesized by microwave-assisted solid-phase synthesis method.  Wang resin or Trt(2-Cl) resin, Fmoc and HBTU-HOBt were used as solid carrier, N-terminal amino acid protecting groups and coupling reagents, respectively.  The ACE inhibitory, α-glucosidase inhibitory, antibacterial and antitumor activities of the synthesized fragments were assayed.  In vitro, Val-Val-Tyr-Pro-Trp-Thr showed high ACE inhibitory activity (IC₅₀ = 7.42 μmol·L⁻¹).  The results indicate that there are two active sites in Val-Val-Tyr-Pro-Trp-Thr-Gln-Arg-Phe, one consists of Val-Val-, and the other -Gln-Arg-Phe.  Peptides showed high ACE inhibitory activity when the N-terminal was hydrophobic amino acid such as Val and C-terminal tripeptide contained Phe, Trp or Arg.  Some of the fragments showed low α-glucosidase inhibitory activity.  No antibacterial activity or antitumor activity was detected in vitro.  The results indicate that these peptides have a potential antihypertensive effect and possible application in the treatment of hypertension.