1.Structural study of poly(beta-benzyl-L-aspartate) monolayers at air-liquid interfaces.
Riou SA1, Hsu SL, Stidham HD. Biophys J. 1998 Nov;75(5):2451-60.
As normally studied, in the solid state or in solution, poly(beta-benzyl-L-aspartate) (PBLA) differs from the other helical polyamino acids in that its alpha-helical conformation is most stable in the left-handed rather than in the right-handed form. The slightly lower energy per residue for the left-handed form in PBLA is easily perturbed, however. The helical screw sense can be inverted in a polar environment and, upon heating above 100 degrees C, a distorted left-handed helix or omega-helix is irreversibly formed. From external reflectance Fourier transform infrared measurements at the air-water interface, the conformation of PBLA in the monolayer state is directly established for the first time. The infrared frequencies of the amide bands suggest that right-handed alpha-helices are formed on the surface of water immediately after spreading the monolayers and independently of the polypeptide conformational distribution in the spreading solution.
2.Solvolysis and aminolysis on peptidyl-Kaiser oxime resin assisted by Ca2+ and Eu3+: a mild procedure to prepare alpha-methyl and -ethyl esters of protected peptides.
Moraes CM1, Bemquerer MP, Miranda MT. J Pept Res. 2000 Apr;55(4):279-88.
Ca2+ and Eu3+ were able to assist solvolysis on peptidyl-Kaiser oxime resins generating alpha-methyl and -ethyl esters of protected peptides. The methanolysis assistance was at least twice as effective as that of acetic acid, the common catalyst used in aminolysis of the ester oxime linkage. No molar excess of Ca2+ or Eu3+ was needed to enhance this reaction efficiency. Ca2+ also assisted aminolysis on peptidyl-Kaiser oxime resins. Solvolysis and aminolysis rates depended on the nature of the C-terminal residue attached to the resin and on the alcohol used. Both reactions were selective to the ester oxime linkage since no significant amount of secondary products, resulting from rearrangements or simultaneous transesterification of the beta-benzyl or cyclohexyl esters, was detected in the reaction media. The alpha-methyl and -ethyl esters of Ac-Ala-Gly-X [where, X = Gly, Ala, Phe or Lys (2-Cl-Z)] and of Ac-Ile-Ser (Bzl)-Asp(OZ) (where, Z = Bzl or cHex) were essentially the only products formed in the solvolyses performed.
3.Transport of amino acid-based prodrugs by the Na+- and Cl(-) -coupled amino acid transporter ATB0,+ and expression of the transporter in tissues amenable for drug delivery.
Hatanaka T1, Haramura M, Fei YJ, Miyauchi S, Bridges CC, Ganapathy PS, Smith SB, Ganapathy V, Ganapathy ME. J Pharmacol Exp Ther. 2004 Mar;308(3):1138-47. Epub 2003 Nov 14.
We evaluated the potential of the Na(+)- and Cl(-)-coupled amino acid transporter ATB(0,+) as a delivery system for amino acid-based prodrugs. Immunofluorescence analysis indicated that ATB(0,+) is expressed abundantly on the luminal surface of cells lining the lumen of the large intestine and the airways of the lung and in various ocular tissues, including the conjunctival epithelium, the tissues easily amenable for drug delivery. We screened a variety of beta-carboxyl derivatives of aspartate and gamma-carboxyl derivatives of glutamate as potential substrates for this transporter using heterologous expression systems. In mammalian cells expressing the cloned ATB(0,+), several of the aspartate and glutamate derivatives inhibited glycine transport via ATB(0,+). Direct evidence for ATB(0,+)-mediated transport of these derivatives was obtained in Xenopus laevis oocytes using electrophysiological methods. Exposure of oocytes, which express ATB(0,+) heterologously, to aspartate beta-benzyl ester as a model derivative induced inward currents in a Na(+)- and Cl(-)-dependent manner with a Na(+)/Cl(-)/aspartate beta-benzyl ester stoichiometry of 2:1:1.
4.1,4-diazepine-2,5-dione ring formation during solid phase synthesis of peptides containing aspartic acid beta-benzyl ester.
Süli-Vargha H1, Schlosser G, Ilas J. J Pept Sci. 2007 Nov;13(11):742-8.
The Fmoc-based SPPS of H-Xaa-Asp(OBzl)-Yaa-Gly-NH(2) sequences results in side reactions yielding not only aspartimide peptides and piperidide derivatives, but also 1,4-diazepine-2,5-dione-peptides. Evidence is presented to show that the 1,4-diazepine-2,5-dione derivative is formed from the aspartimide peptide. The rate of this ring transformation depends primarily on the tendency to aspartimide and piperidide formation, which is influenced by the nature of the amino acid following the aspartic acid beta-benzyl ester (Xaa). However the bulkiness of the amino acid side chain preceeding the aspartic acid beta-benzyl ester (Yaa) is also important. Under certain conditions the 1,4-diazepine-2,5-dione peptide derivative may even be formed dominantly, which is a highly undesirable side reaction in peptide synthesis, but which provides a new way for the synthesis of diazepine peptide derivatives with targeted biological or pharmacological activity.
