1.Ring size in cyclic endomorphin-2 analogs modulates receptor binding affinity and selectivity.
Piekielna J1, Kluczyk A, Gentilucci L, Cerlesi MC, Calo' G, Tomböly C, Łapiński K, Janecki T, Janecka A. Org Biomol Chem. 2015 Jun 7;13(21):6039-46. doi: 10.1039/c5ob00565e.
The study reports the solid-phase synthesis and biological evaluation of a series of new side chain-to-side chain cyclized opioid peptide analogs of the general structure Tyr-[D-Xaa-Phe-Phe-Asp]NH2, where Xaa = Lys (1), Orn (2), Dab (3), or Dap (4) (Dab = 2,4-diaminobutyric acid, Dap = 2,3-diaminopropionic acid), containing 17- to 14-membered rings. The influence of the ring size on binding to the MOP, DOP and KOP opioid receptors was studied. In general, the reduction of the size of the macrocyclic ring increased the selectivity for the MOP receptor. The cyclopeptide incorporating Xaa = Lys displayed subnanomolar MOP affinity but modest selectivity over the KOP receptor, while the analog with the Orn residue showed increased affinity and selectivity for MOP. The analog with Dab was a weak MOP agonist and did not bind to the other two opioid receptors. Finally, the peptide with Xaa = Dap was completely MOP receptor-selective with subnanomolar affinity.
2.The Cu²⁺ binding properties of branched peptides based on L-2,3-diaminopropionic acid.
Szyrwiel Ł1, Szczukowski Ł, Pap JS, Setner B, Szewczuk Z, Malinka W. Inorg Chem. 2014 Aug 4;53(15):7951-9. doi: 10.1021/ic5007428. Epub 2014 Jul 14.
Three new branched peptides, namely, H-Gly-Dap(H-Gly)-Gly-NH2 (3G), H-His-Dap(H-His)-Gly-NH2 (2HG), and H-Gly-Dap(H-Gly)-His-NH2 (2GH), where Dap stands for the 2,3-diaminopropionic acid residue, were synthesized by solid phase procedures. Because of the junction at Dap these peptides have three available pending arms for metal chelation. The complex formation between these peptides and 1 equiv of Cu(2+) was investigated as a function of pH by potentiometry ultraviolet-visible absorption, circular dichroism, and X-band electron paramagnetic resonance spectroscopy in aqueous medium. Our results clearly demonstrate that cooperation between all three peptide arms essentially contributes to the stability of copper(II) complexes.
3.Inhalable dry powder formulations of siRNA and pH-responsive peptides with antiviral activity against H1N1 influenza virus.
Liang W1, Chow MY, Lau PN, Zhou QT, Kwok PC, Leung GP, Mason AJ, Chan HK, Poon LL, Lam JK. Mol Pharm. 2015 Mar 2;12(3):910-21. doi: 10.1021/mp500745v. Epub 2015 Jan 30.
Pulmonary delivery of siRNA has considerable therapeutic potential for treating viral respiratory infectious diseases including influenza. By introducing siRNA that targets the conserved region of viral genes encoding nucleocapsid protein (NP), viral mRNAs can be degraded and viral replication can be inhibited in mammalian cells. To enable siRNA to be used as an antiviral agent, the nucleic acid delivery barrier must be overcome. Effective local delivery of siRNA to lung tissues is required to reduce the therapeutic dose and minimize systemic adverse effects. To develop a formulation suited for clinical application, complexes of pH-responsive peptides, containing either histidine or 2,3-diaminopropionic acid (Dap), and siRNA were prepared into dry powders by spray drying with mannitol, which was used as a bulking agent. The spray-dried (SD) powders were characterized and found to be suitable for inhalation with good stability, preserving the integrity of the siRNA as well as the biological and antiviral activities.
4.Diaminopropionic Acid Reinforced Graphene Sponge and Its Use for Hemostasis.
Quan K1, Li G1, Tao L2, Xie Q3, Yuan Q1, Wang X1. ACS Appl Mater Interfaces. 2016 Mar 30;8(12):7666-73. doi: 10.1021/acsami.5b12715. Epub 2016 Mar 15.
2,3-Diaminopropionic acid (DapA), a medicinal amino acid, is used for the first time to prepare a DapA cross-linked graphene sponge (DCGS) for hemostasis treatment. In a comparison with the reported ethanediamine (EDA) cross-linked graphene sponge (CGS), this carboxyl-functionalized DCGS can not only quickly absorb plasma, but also stimulate erythrocytes and platelets to change their normal form and structure at the interface, which largely affects a cell's metabolism and biofunction, thus further promoting blood coagulation. Whole blood clotting and rat-tail amputation tests indicated that on the basis of the additional interfacial stimulation, the hemostatic efficiency of the DCGS has been significantly improved in comparison with that of the CGS control (P < 0.05). In-depth insight revealed that the increased oxidation degree and the negative charge density play the crucial rule in the enhanced hemostatic performance. The chiral effect contributes mainly to the selective adhesion of erythrocytes and platelets rather than practical hemostasis.
