Antihypertensive Properties of Spinach Leaf Protein Digests

Leaf protein containing approximately 50% rubisco (ribulose bisphosphate carboxylase/oxygenase) was obtained from fresh spinach leaf with the use of a simple extraction method. Pepsin and pepsin−pancreatin digests of spinach leaf protein have potent angiotensin-I converting enzyme inhibitory properties with IC50 values of 56 and 120 μg/mL, respectively. Both digests of leaf protein have antihypertensive effects after oral administration to spontaneously hypertensive rats (SHR) with minimum effective doses of 0.25 and 0.5 g/kg, respectively. The maximum antihypertensive effect for the pepsin digest was observed 4 h after oral administration, while for the pepsin−pancreatin digest, the maximum effect was observed 2 h after oral administration. Undigested spinach leaf protein did not exert any significant antihypertensive effect after oral administration to SHR at doses of 0.5 and 1 g/kg. Obtained results show that the pepsin digest of leaf protein may be useful in treatment of hypertension. Keywords: Leaf protein isolation; spinach; leaf protein digest; ACE inhibitors; antihypertensive effect; spontaneously hypertensive ra

Influence of the Side Chain Next to C-Terminal Benzimidazole in Opioid Pseudopeptides Containing the Dmt-Tic Pharmacophore

To improve the structure−activity studies of the lead δ opioid agonist H-Dmt-Tic-Asp*-Bid, we synthesized and pharmacologically characterized a series of analogues in which the side chain next to 1H-benzimidazole-2-yl (Bid) was substituted by those endowed with different chemical properties. Interesting results were obtained: (1) only Gly, Ala, and Asp resulted in δ agonism, (2) Phe yielded δ antagonism, (3) and all other residues except Glu (devoid of any activity) gave μ agonism

Further Studies on Lead Compounds Containing the Opioid Pharmacophore Dmt-Tic

Some reference opioids containing the Dmt-Tic pharmacophore, especially the δ agonists H-Dmt-Tic-Gly-NH-Ph (1) and H-Dmt-Tic-NH-(S)CH(CH2−COOH)-Bid (4) (UFP-512) were evaluated for the influence of the substitution of Gly with aspartic acid, its chirality, and the importance of the −NH-Ph and N1H-Bid hydrogens in the inductions of δ agonism. The results provide the following conclusions: (i) Asp increases δ selectivity by lowering the μ affinity; (ii) −NH-Ph and N1H-Bid nitrogens methylation transforms the δ agonists into δ antagonists; (iii) the substitution of Gly with l-Asp/d-Asp in the δ agonist H-Dmt-Tic-Gly-NH-Ph gave δ antagonists; the same substitution in the δ agonist H-Dmt-Tic-NH-CH2−Bid yielded more selective agonists, H-Dmt-Tic-NH-(S)CH(CH2−COOH)-Bid and H-Dmt-Tic-NH-(R)CH(CH2−COOH)-Bid; (iv) l-Asp seems important only in functional bioactivity, not in receptor affinity; (v) H-Dmt-Tic-NH-(S)CH(CH2−COOH)-Bid(N1-Me) (10) evidenced analgesia similar to 4, which was reversed by naltrindole only in the tail flick. 4 and 10 had opposite behaviours in mice; 4 caused agitation, 10 gave sedation and convulsions