Synthesis of Novel Peptides Using Unusual Amino Acids.

Small peptides are valuable peptides due to their extended biological activities. Their activities could be categorized according to their low antigenicity, osmotic pressure, and also because of their astonishing bioactivities. For example, the aggression of Phe-Phe fibers via self-assembly and intermolecular hydrogen bonding is the main reason for the formation of Alzheimer's ß-amyloid fibrils. Hydrogen bonding is the main intramolecular interaction in peptides, while the presence of aromatic ring leads to the π-π stacking and affects the self-assembly and aggression. Thus, insertion of an unusual amino acid into peptide sequence facilitates the formation of intramolecular bonds, lipophilicity and its conformation. To design new small peptides with remarkable lipophilicity, it is an idea to employ γ-amino acid, such as gabapentin (H2N-Gpn-OMe) and baclofen (H2N-Baclofen-OMe), in the structure of small peptides to increase cell-penetrating properties and to prevent aggression of Phe-Phe fibrils in ß-amyloids of Alzheimer's disease. Some new tri- and tetrapeptides were synthesized through introducing biologically active gabapentin and baclofen to dipeptide of phenylalanine (Phe-Phe) through solution phase peptide synthesis strategy.

Synthesis of novel Gn-RH analogues using Ugi-4MCR.

An efficient method for the synthesis of some Gn-RH analogues based on Ugi reaction has been developed. Four-component reaction of N- and C-terminus peptides, aromatic aldehydes and isocyanides affords novel Gn-RH analogues derived from triptorelin and gonadorelin. All of the products were purified using preparative HPLC and the structures were assigned according to MALDI-mass spectrometry data.

Efficient Synthesis of Norbuprenorphines Coupled with Enkephalins and Investigation of Their Permeability.

An efficient approach for the synthesis of norbuprenorphin derivatives through coupling of enkephalins and norbuprenorphine intermediates is described. Norbuprenorphine derivative was synthesized from thebaine and then, its reaction with succinic acid and phthalic acid was also studied. Meanwhile, the synthesis of enkephalins was done using solid phase peptide synthesis approach. Furthermore, after cleavage of the peptide from the surface of the resin, the coupling of enkephalins with norbuprenorphine derivative was done using TBTU as a coupling reagent then the derivatives were purified using preparative high-pressure liquid chromatography and their structures were confirmed using high-resolution mass spectrometry data. Later, their permeability across membranes was investigated. After PAMPA studies, it was found that the permeability of all norbuprenorphin-enkephalin derivatives was increased; however, succinic and phthalic acid derivatives showed higher permeability than norbuprenorphine-Leu-enkephalin.

Anticancer activity of a new gonadotropin releasing hormone analogue.

Gonadotropin releasing hormone (GnRH) has a pivotal role in the biology of reproduction processes. In extrapituitary compartments GnRH and its receptor act as a part of the autocrin regulatory system of cell proliferation, resulting in its anticancer activity. Here the anticancer activity of a new analogue of GnRH has been investigated. Results indicate that proliferation of human breast and ovarian cancer cell lines is dose-dependently inhibited. The inhibitory efficiency of this new analogue is proved to be higher than the original triptorelin. In addition to its antimitogenic activity, evidence was found for the involvement of the apoptotic mechanism in the action of the new analogue. Furthermore the presence of chemical groups in the peptide sequence is thought to increase the protease stability of the new analogue in comparison with triptorelin. Consequently our new analogue can be considered as a good pharmaceutical candidate.