1. Insertion of the Asp-Ser/Phe sequence in the P' position of hirutonin provides molecules having both antithrombin and disintegrin activity
L Leblond, J DiMaio, P D Winocour Thromb Res. 1999 Feb 15;93(4):171-81. doi: 10.1016/s0049-3848(98)00182-0.
We have developed novel synthetic peptides that display both antithrombin and disintegrin activity. These peptides were derived from hirutonins, a class of potent proteolytically resistant thrombin inhibitors, in which a dipeptidyl sequence, Asp-Phe or Asp-Ser, was introduced after the proteolytically resistant ketomethylene arginyl glycine isostere. These modified hirutonins inhibited the amidolytic activity of alpha-thrombin (Ki approximately 35 nM), prevented fibrinogen clotting (dTT approximately 100 nM) and inhibited human platelet aggregation and 5-hydroxytryptamine secretion induced by alpha-thrombin (IC50 approximately 600 nM). Unlike their parent hirutonins, they inhibited SFLLR-NH2-induced human platelet aggregation (IC50 approximately 45 microM) without inhibition of 5-HT secretion. These peptides also competed for fibrinogen binding to purified GpIIbIIIa integrin (IC50 approximately microM) and prevented attachment of B16-F10 mouse melanoma cells to vitronectin. We conclude that addition of the dipeptidyl sequence, Asp-Phe or Asp-Ser, in hirutonin molecules confers disintegrin activity. However, this activity was not superior to the activity observed with the linear RGDS peptide and was achieved at the expense of direct antithrombin activity. Additional modifications around the RGD-like adhesion sequence may permit identification of the appropriate conformation for optimal binding to thrombin and to specific integrin receptors.
2. Transepithelial Transport Route and Liposome Encapsulation of Milk-Derived ACE-Inhibitory Peptide Arg-Leu-Ser-Phe-Asn-Pro
Tao Zhang, Mi Su, Xiaoxiao Jiang, Yiqiu Xue, Jiaxin Zhang, Xiaoqun Zeng, Zhen Wu, Yuxing Guo, Daodong Pan J Agric Food Chem. 2019 May 15;67(19):5544-5551. doi: 10.1021/acs.jafc.9b00397. Epub 2019 May 6.
The purpose of the study was to investigate the transepithelial transport route of Arg-Leu-Ser-Phe-Asn-Pro (RLSFNP), a milk-derived angiotensin-converting enzyme (ACE) inhibitory peptide, and to encapsulate RLSFNP in a liposome to improve its intestinal bioavailability. The transport route was investigated using transport inhibitors in a human intestinal Caco-2 cell monolayer model. Sodium azide and wortmannin significantly reduced the permeability of RLSFNP ( P < 0.01), indicating that energy-dependent transcytosis is involved in the transport of RLSFNP across Caco-2 cells. The hexapeptide RLSFNP was then embedded in liposomes, and the RLSFNP liposome was characterized. Afterward, the cellular uptake and transepithelial transport ability of the RLSFNP liposome across Caco-2 cell monolayers was observed. The results demonstrated that the RLSFNP liposome was successfully prepared, having a significant sustained release and storage capability. The RLSFNP liposome can be absorbed by Caco-2 cells, with an increased intestinal absorption of RLSFNP compared to RLSFNP alone. The results showed a new way to improve RLSFNP intestinal bioavailability.
3. L-serine tripeptides: Ac-Ser-Gly, Ala-Ser-Gly and Gly-Ser-Phe
L Pogliani, D Ziessow Int J Pept Protein Res. 1983 Aug;22(2):148-53. doi: 10.1111/j.1399-3011.1983.tb02079.x.
The 1H and 13C n.m.r. spectra of Ac-Ser-Gly, Ala-Ser-Gly and Gly-Ser-Phe tripeptides have been measured and analysed at three different pD values. The n.m.r. parameters of Ser side-chain are nearly pD independent. C alpha H group (13C/1H) of Ser residue of Gly-Ser-Phe shows a consistent pD dependence in acid solutions. Conformational calculations on Ser side-chain show the growing importance of the gauche conformers on the overall conformation of the side-chain all along the three tripeptides.
