Glòria Sanclimens

Solid‐phase synthesis of second‐generation polyproline dendrimers

Second‐generation dendrimers have been prepared on solid phase by successive additions of branched polyproline building blocks starting from two different branching units anchored to the solid support. The preparation of Pro‐rich building blocks was carried out by stepwise solid‐phase synthesis and their iterative addition was performed by a convergent approach, also using solid‐phase synthesis. cis‐4‐Amino‐L‐proline and imidazolidine‐2‐carboxylic acid were used as branching units due to their structural resemblance to proline. The optimized strategy allowed the target compounds to be obtained with high purities without the need for purification steps.

Neurotoxicity of Prion Peptides Mimicking the Central Domain of the Cellular Prion Protein

The physiological functions of PrPC remain enigmatic, but the central domain, comprising highly conserved regions of the protein may play an important role. Indeed, a large number of studies indicate that synthetic peptides containing residues 106–126 (CR) located in the central domain (CD, 95–133) of PrPC are neurotoxic. The central domain comprises two chemically distinct subdomains, the charge cluster (CC, 95–110) and a hydrophobic region (HR, 112–133). The aim of the present study was to establish the individual cytotoxicity of CC, HR and CD. Our results show that only the CD peptide is neurotoxic. Biochemical, Transmission Electron Microscopy and Atomic Force Microscopy experiments demonstrated that the CD peptide is able to activate caspase-3 and disrupt the cell membrane, leading to cell death.

Branched Poly(proline) Peptides: An Efficient New Approach to the Synthesis of Repetitive Branched Peptides

Proline is unique among the twenty genetically coded amino acids in that it contains both a cyclic backbone and a secondary α-amino group. These structural features impart unique stereochemical properties on proline. Poly(proline) oligomers exist in two distinct conformations in solution. In organic solvents they tend to adopt a conformation known as poly(proline) I (PPI), whereas in aqueous solvents they tend to adopt a different conformation known as poly(proline) II (PPII). We report here a new family of branched poly(proline) peptides. After a careful study of the different approaches, an efficient protocol for the synthesis of this kind of peptide has been established. cis-4-Amino-L-proline was mainly used as a branching unit in order to minimize its effects on the conformation of the rest of the molecule. The synthetic strategy employed was based on a convergent solid-phase peptide synthesis methodology that gave crude peptides that were easy to purify. This approach provides a new method for the synthesis of other repetitive branched peptides, minimizing not only synthetic difficulties but also purification problems. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Saturated resins or stress of the resin

Although the solid-phase mode is an excellent strategy for the preparation of both biomolecules and small molecules, the synthesis of polyproline-based dendrimers has provided evidence that the capacity of the bead is limited. This phenomenon, which can be interpreted as saturation or stress of the resin, can lead to a complete breakdown of the bead structure.

Proline: A Key Building Block in “de novo” Designed Peptide Molecules

Proline is unique among the proteinogenic amino acids in that it has a disubstituted amino group. Living systems have taken advantage of this in a variety of ways, especially in molecular recognition processes [1]. Could proline play a special role in the “de novo” design of peptides or proteins? Recent work that we present here indicates that this could indeed be the case.