Cleavage of protected amino acids and peptides from the new o-nitrogenzoyl polyethylene glycol support by catalytic hydrogenolysis

Catalytic hydrogenolysis as a cleavage method for removal of protected amino acids and peptides from the 3-nitro-4-bromonethylbenzoyl polyethylene glycol support used in liquid-phase peptide synthesis is demonstrated.     

Fluorinated peptidomimetics: synthesis, conformational and biological features

Peptides modified with fluoroalkyl functions in key backbone positions have been scarcely studied so far. Thus, little is known about their synthesis, their structural and physico-chemical properties, and their biological features. Our interest in this field of research led to the development of stereocontrolled synthetic protocols, both in solution and in solid phase, for many different fluoroalkyl peptidomimetics, some of which are overviewed in this paper: (a) ψ[CH(CF₃)NH]-peptide mimics holding a great potential as hybrids between natural peptides and hydrolytic transition state analogs; (b) trifluoromethyl (Tfm) malic peptidomimetics as micromolar inhibitors of some matrix metalloproteinases; (c) bis-Tfm analogs of Pepstatin A, that are nanomolar and selective inhibitors of the protozoal aspartyl protease Plasmepsin II.     

Synthesis of an olefin-containing cyclic peptide using the solid-phase Horner-Emmons reaction

Linear and cyclic olefin peptides containing the substrate sequence for human T-cell leukemia virus type-1 (HTLV-1) were efficiently synthesized on a solid support using the Horner-Emmons reaction. The precursor peptide aldehyde was prepared by oxidation of the corresponding peptide alcohol with Dess-Martin periodinane. The oxidation reaction proceeded quantitatively on a cross-linked ethoxylate acrylate resin (CLEAR) support instead of a polystyrene-based support. Cyclization on the solid support was achieved via an amide bond formation mediated by EDC/HOAt to yield a single major product. The linear olefin peptide was cleaved by HTLV-1 protease at the scissile site, whereas the cyclic olefin peptide functions as a competitive inhibitor rather than a substrate.     

Microwave-assisted guanidinylation in solid phase peptide synthesis: comparison of various reagents

The guanidinylation of a peptide chain on a polymeric support under microwave conditions using derivatives of thioureas—S-alkylisothioureas, pyrazole-carboxamidine, and guanidine as guanidinylating reagents is described. The best results are obtained with N,N′-di-Z-S-methylisothiourea and N,N′-di-Z(2-Cl)-S-methylisothiourea. It is found that guanidinylation with reagents containing Boc groups is accompanied by side reactions.